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Dumolard L, Gerster T, Chuffart F, Decaens T, Hilleret MN, Larrat S, Saas P, Jouvin-Marche E, Durantel D, Marche PN, Macek Jilkova Z, Aspord C. HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients' clinical stage. Hepatol Commun 2025; 9:e0625. [PMID: 39878655 PMCID: PMC11781764 DOI: 10.1097/hc9.0000000000000625] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 09/25/2024] [Indexed: 01/31/2025] Open
Abstract
BACKGROUND Hepatitis B is a liver infection caused by HBV. Infected individuals who fail to control the viral infection develop chronic hepatitis B and are at risk of developing life-threatening liver diseases, such as cirrhosis or liver cancer. Dendritic cells (DCs) play important roles in the immune response against HBV but are functionally impaired in patients with chronic hepatitis B. The underlying mechanisms involved in HBV-induced DC dysfunctions remain to be elucidated. METHODS We explored DC modulations by HBV and HBsAg by exposing blood-derived cDC1s, cDC2s, and plasmacytoid DCs from healthy donors to HBV or HBsAg and stimulating them with toll-like receptor ligand. Their phenotypic and functional features, as well as their metabolic profile, were analyzed through multiparametric flow cytometry and multiplex assays and further explored on patients' samples. RESULTS We found that HBV deeply reshaped the DC secretome in response to toll-like receptor ligand. Strikingly, we observed that HBV-exposed DCs secrete high levels of CX3CL1 (fractalkine), a chemokine responsible for attracting antiviral effectors to the site of infection. HBsAg exposure favored DC activation while drastically altering TRAIL expression in response to toll-like receptor ligand and increasing the secretion of cytokines/chemokines involved in immune tolerance. HBsAg further dampened the metabolism of DC subsets while driving metabolic switches. Notably, the relevance of the CX3CL1/CX3CR1 axis, TGF-β, and metabolic disturbances was demonstrated within intrahepatic DC subsets in patients according to disease stage. CONCLUSIONS Our work brings new insights into the immunomodulation induced by HBV on DCs, which contribute to impaired antiviral responses and progression toward chronicity.
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Affiliation(s)
- Lucile Dumolard
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France
| | - Theophile Gerster
- Hepato-Gastroenterology and Digestive Oncology Department, CHU Grenoble Alpes, Grenoble, France
- Etablissement Français du Sang Auvergne-Rhone-Alpes, R&D Laboratory, Grenoble, France
| | - Florent Chuffart
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France
| | - Thomas Decaens
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France
- Hepato-Gastroenterology and Digestive Oncology Department, CHU Grenoble Alpes, Grenoble, France
| | - Marie-Noelle Hilleret
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France
- Hepato-Gastroenterology and Digestive Oncology Department, CHU Grenoble Alpes, Grenoble, France
| | - Sylvie Larrat
- University Grenoble Alpes, Laboratoire de Virologie, CHU Grenoble Alpes, Grenoble, France
| | - Philippe Saas
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France
- Etablissement Français du Sang Auvergne-Rhone-Alpes, R&D Laboratory, Grenoble, France
| | - Evelyne Jouvin-Marche
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France
| | - David Durantel
- INSERM, U1111, Centre International de Recherche en Infectiologie (CIRI), University of Lyon (UCBL1), CNRS UMR_5308, ENS de Lyon, Lyon, France
| | - Patrice N. Marche
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France
| | - Zuzana Macek Jilkova
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France
- Hepato-Gastroenterology and Digestive Oncology Department, CHU Grenoble Alpes, Grenoble, France
| | - Caroline Aspord
- University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Institute for Advanced Biosciences, Grenoble, France
- Etablissement Français du Sang Auvergne-Rhone-Alpes, R&D Laboratory, Grenoble, France
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2
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Mak LY, Boettler T, Gill US. HBV Biomarkers and Their Role in Guiding Treatment Decisions. Semin Liver Dis 2024; 44:474-491. [PMID: 39442530 DOI: 10.1055/a-2448-4157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
Over 300 million individuals worldwide are chronically infected with hepatitis B virus and at risk for progressive liver disease. Due to the lack of a therapy that reliably achieves viral elimination and the variability of liver disease progression, treatment decisions are guided by the degree of liver disease and viral biomarkers as the viral life-cycle is well characterized and largely conserved between individuals. In contrast, the immunological landscape is much more heterogeneous and diverse and the measurement of its components is less well standardized. Due to the lack of a universal and easily measurable set of biomarkers, clinical practice guidelines remain controversial, aiming for a balance between simplifying treatment decisions by reducing biomarker requirements and using all available biomarkers to avoid overtreatment of patients with low risk for disease progression. While approved therapies such as nucleos(t)ide analogs improve patient outcomes, the inability to achieve a complete cure highlights the need for novel therapies. Since no treatment candidate has demonstrated universal efficacy, biomarkers will remain important for treatment stratification. Here, we summarize the current knowledge on virological and immunological biomarkers with a specific focus on how they might be beneficial in guiding treatment decisions in chronic hepatitis B.
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Affiliation(s)
- Lung-Yi Mak
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
- Department of Medicine, Queen Mary Hospital, School of Clinical Medicine, The Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Tobias Boettler
- Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Upkar S Gill
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
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3
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Elgendy DI, Othman AA, Eid MM, El-Kowrany SI, Sallam FA, Mohamed DA, Zineldeen DH. The impact of β-glucan on the therapeutic outcome of experimental Trichinella spiralis infection. Parasitol Res 2023; 122:2807-2818. [PMID: 37737322 PMCID: PMC10667415 DOI: 10.1007/s00436-023-07964-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Accepted: 09/02/2023] [Indexed: 09/23/2023]
Abstract
Trichinellosis is a cosmopolitan zoonosis that is caused mainly by Trichinella spiralis infection. The human disease ranges from mild to severe and fatality may occur. The treatment of trichinellosis still presents a challenge for physicians. Anti-inflammatory drugs are usually added to antiparasitic agents to alleviate untoward immuno-inflammatory responses and possible tissue damage but they are not without adverse effects. Thus, there is a need for the discovery of safe and effective compounds with anti-inflammatory properties. This study aimed to evaluate the activity of β-glucan during enteral and muscular phases of experimental T. spiralis infection as well as its therapeutic potential as an adjuvant to albendazole in treating trichinellosis. For this aim, mice were infected with T. spiralis and divided into the following groups: early and late β-glucan treatment, albendazole treatment, and combined treatment groups. Infected mice were subjected to assessment of parasite burden, immunological markers, and histopathological changes in the small intestines and muscles. Immunohistochemical evaluation of NF-κB expression in small intestinal and muscle tissues was carried out in order to investigate the mechanism of action of β-glucan. Interestingly, β-glucan potentiated the efficacy of albendazole as noted by the significant reduction of counts of muscle larvae. The inflammatory responses in the small intestine and skeletal muscles were mitigated with some characteristic qualitative changes. β-glucan also increased the expression of NF-κB in tissues which may account for some of its effects. In conclusion, β-glucan showed a multifaceted beneficial impact on the therapeutic outcome of Trichinella infection and can be regarded as a promising adjuvant in the treatment of trichinellosis.
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Affiliation(s)
- Dina I Elgendy
- Medical Parasitology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Ahmad A Othman
- Medical Parasitology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
| | - Mohamed M Eid
- Medical Parasitology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Samy I El-Kowrany
- Medical Parasitology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Fersan A Sallam
- Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Dareen A Mohamed
- Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Doaa H Zineldeen
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
- College of Medicine, Sulaiman AlRajhi University, 51942, Albukairiyah, Saudi Arabia
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4
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You H, Wang X, Ma L, Zhang F, Zhang H, Wang Y, Pan X, Zheng K, Kong F, Tang R. Insights into the impact of hepatitis B virus on hepatic stellate cell activation. Cell Commun Signal 2023; 21:70. [PMID: 37041599 PMCID: PMC10088164 DOI: 10.1186/s12964-023-01091-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 02/26/2023] [Indexed: 04/13/2023] Open
Abstract
During chronic hepatitis B virus (HBV) infection, hepatic fibrosis is a serious pathological condition caused by virus-induced liver damage. The activation of hepatic stellate cells (HSCs) is a central event in the occurrence and progression of liver fibrosis. Although accumulating evidence has shown that HBV directly stimulates HSC activation, whether the virus infects and replicates in HSCs remains controversial. Inflammation is one of the obvious characteristics of chronic HBV infection, and it has been demonstrated that persistent inflammation has a predominant role in triggering and maintaining liver fibrosis. In particular, the regulation of HSC activation by HBV-related hepatocytes via various inflammatory modulators, including TGF-β and CTGF, in a paracrine manner has been reported. In addition to these inflammation-related molecules, several inflammatory cells are essential for the progression of HBV-associated liver fibrosis. Monocytes, macrophages, Th17 cells, NK cells, as well as NKT cells, participate in the modulation of HBV-related liver fibrosis by interacting with HSCs. This review summarizes current findings on the effects of HBV and the relevant molecular mechanisms involved in HSC activation. Because HSC activation is essential for liver fibrosis, targeting HSCs is an attractive therapeutic strategy to prevent and reverse hepatic fibrosis induced by HBV infection. Video abstract.
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Affiliation(s)
- Hongjuan You
- Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Xing Wang
- Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Lihong Ma
- Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Fulong Zhang
- Imaging Department, The Second Affiliated Hospital of Shandong First Medical University, Taian, China
| | - Huanyang Zhang
- Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yuxin Wang
- Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Xiucheng Pan
- Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Kuiyang Zheng
- Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China
- National Demonstration Center for Experimental Basic Medical Sciences Education, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Fanyun Kong
- Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
| | - Renxian Tang
- Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
- National Demonstration Center for Experimental Basic Medical Sciences Education, Xuzhou Medical University, Xuzhou, Jiangsu, China.
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Wang Q, Qian H, Liu X, Jiang J, Hao Q. Plasma cytokine profile in occult HBV-infected blood donors. Future Virol 2023. [DOI: 10.2217/fvl-2022-0193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
Aim: Cytokine profile in occult HBV infection (OBI) was systematically investigated to identify the immunopathogenesis of OBI. Materials & methods: A total of 46 OBI, ten asymptomatic hepatitis B surface antigen carriers, ten chronic hepatitis B and 12 healthy blood donors were recruited. A total of 21 plasma cytokines were detected. Results: Compared with healthy blood donors, elevated plasma Th1, Th2, Th17 and immune regulatory associated cytokines were observed in OBI. Almost no significant difference was found for these cytokines among OBI, asymptomatic hepatitis B surface antigen carriers and chronic hepatitis B. OBI displayed the predominance of type 2 and regulatory immunity. Conclusion: OBI displayed the general cytokine profile of chronic HBV infection, which might contribute to virus persistence and the presence of the liver microinflammatory environment. The clinical implications of OBI deserve more attention.
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Affiliation(s)
- Qinghui Wang
- Department of Clinical Laboratory, Wuxi Blood Center, Wuxi, 214000, China
| | - Huizhong Qian
- Department of Clinical Laboratory, Wuxi Blood Center, Wuxi, 214000, China
| | - Xiao Liu
- Department of Clinical Laboratory, Wuxi Blood Center, Wuxi, 214000, China
| | - Jian Jiang
- Department of Clinical Laboratory, Wuxi Blood Center, Wuxi, 214000, China
| | - Qingqin Hao
- Department of Clinical Laboratory, Wuxi Blood Center, Wuxi, 214000, China
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Cai X, Zha H, Yang Z, Du Y, Dai X, Yang B, Wang J, He Q, Weng Q. Genetic dominance of transforming growth factor-β1 polymorphisms in chronic liver disease. Front Immunol 2022; 13:1058532. [DOI: 10.3389/fimmu.2022.1058532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 10/31/2022] [Indexed: 11/17/2022] Open
Abstract
Chronic liver disease (CLD) is an extremely common clinical condition accompanied by sustained inflammatory response leading to tissue damage. Transforming growth factor-β1 (TGF-β1) is known as a master immune regulator in CLDs, but the association between TGF-β1 polymorphisms and CLD risk is controversial and inconclusive, and the genetic dominance of CLDs remains unknown. In this study, the relationship between TGF-β1 polymorphisms and CLD susceptibility is systematically analyzed based on 35 eligible studies. Individuals with the TGF-β1-509 allele (TT or CT) or codon 10 allele (Pro/Pro) show an increased risk of CLDs. Subgroup analyses indicate TGF-β1-509C/T has a significant correlation with cirrhosis and chronic hepatitis C, codon 10 is associated with chronic hepatitis B occurrence, and codon 25 exhibits a relationship with autoimmune hepatitis risk. Missense mutations in G29E, A105S, D191N, and F321L of TGF-β1 are the genetic factors of HCC susceptibility. Furthermore, the TGF-β1 gene expression is significantly elevated in CLD patients, and the TGF-β1 codon 263 is located close to the region where the TGF-β1 dimerization interacts, indicating the TGF-β1 codon 263 variant may affect the secretion of TGF-β1 by altering its dimerization. Together, our findings provide new insights into the immune regulator gene TGF-β1 polymorphisms as susceptibility factors for CLD occurrence and regulators for TGF-β1 expression, which have implications for the regulation of immune factors during CLD development.
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7
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Park ES, Dezhbord M, Lee AR, Park BB, Kim KH. Dysregulation of Liver Regeneration by Hepatitis B Virus Infection: Impact on Development of Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:cancers14153566. [PMID: 35892823 PMCID: PMC9329784 DOI: 10.3390/cancers14153566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/19/2022] [Accepted: 07/21/2022] [Indexed: 02/04/2023] Open
Abstract
The liver is unique in its ability to regenerate in response to damage. The complex process of liver regeneration consists of multiple interactive pathways. About 2 billion people worldwide have been infected with hepatitis B virus (HBV), and HBV causes 686,000 deaths each year due to its complications. Long-term infection with HBV, which causes chronic inflammation, leads to serious liver-related diseases, including cirrhosis and hepatocellular carcinoma. HBV infection has been reported to interfere with the critical mechanisms required for liver regeneration. In this review, the studies on liver tissue characteristics and liver regeneration mechanisms are summarized. Moreover, the inhibitory mechanisms of HBV infection in liver regeneration are investigated. Finally, the association between interrupted liver regeneration and hepatocarcinogenesis, which are both triggered by HBV infection, is outlined. Understanding the fundamental and complex liver regeneration process is expected to provide significant therapeutic advantages for HBV-associated hepatocellular carcinoma.
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Affiliation(s)
- Eun-Sook Park
- Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Seoul 05029, Korea; (E.-S.P.); (B.B.P.)
| | - Mehrangiz Dezhbord
- Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Korea; (M.D.); (A.R.L.)
| | - Ah Ram Lee
- Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Korea; (M.D.); (A.R.L.)
| | - Bo Bae Park
- Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Seoul 05029, Korea; (E.-S.P.); (B.B.P.)
| | - Kyun-Hwan Kim
- Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon 16419, Korea; (M.D.); (A.R.L.)
- Correspondence: ; Tel.: +82-31-299-6126
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8
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Qiu H, Wang N, Lin D, Yuan Y, Li J, Mao D, Meng Y. The positive feedback loop of furin and TGFβ1 enhances the immune responses of Tregs to hepatocellular carcinoma cells and hepatitis B virus in vitro. Cell Biol Int 2022; 46:1215-1226. [PMID: 35349767 DOI: 10.1002/cbin.11806] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 03/14/2022] [Accepted: 03/24/2022] [Indexed: 11/06/2022]
Abstract
Regulatory T cells (Tregs) can exert immunosuppressive activity. Furin can regulate Treg functions, hepatitis B virus (HBV) persistent infection, and hepatocellular carcinoma (HCC) development. However, it remains unknown whether furin can regulate the immune responses of Tregs to HBV and HCC cells. Here, coculture systems of HBV1.3P-HepG2.3P-HepG2 cells and Tregs transduced with or without lentiviral particles that could overexpress furin or knockdown furin/transforming growth factor β1 (TGFβ1) were established to investigate the regulatory relationship between furin and TGFβ1 and the effect of furin/TGFβ1 on Treg activity. Also, the effects of furin overexpression or furin/TGFβ1 knockdown in Tregs on the immunological activity of effector T cells (Teffs)/cytotoxic T lymphocytes (CTLs) and HBV replication/expression were explored in the coculture system of Teff/CTL, Treg, and HBV1.3P-HepG2 cells. Our results showed that furin expression and TGFβ1 secretion were notably increased in Tregs, and Furin and TGFβ1 formed a positive feedback loop to activate Tregs in the coculture system of Tregs and HBV1.3P-HepG2 cells. Furin or TGFβ1 knockdown in Tregs promoted Teff cell proliferation, stimulated interleukin-2 and interferon-γ secretion, and inhibited HBV replication/gene expression in the coculture system of Teff, Treg, and HBV1.3P-HepG2 cells. Moreover, furin or TGFβ1 depletion in Tregs enhanced the killing activity of CTLs against HBV1.3P-HepG2 cells and curbed HBV replication/gene expression in the coculture system of Tregs, CTLs, and HBV1.3P-HepG2 cells. In conclusion, the positive feedback loop of furin and TGFβ1 enhanced the immune responses of Tregs to HCC cells and HBV in vitro.
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Affiliation(s)
- Hua Qiu
- Department of Chinese Medicine (CM), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Na Wang
- Department of Live Disease, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Dongyi Lin
- Department of Chinese Medicine (CM), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Ying Yuan
- Department of Chinese Medicine (CM), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Jinyuan Li
- Department of Chinese Medicine (CM), Guangxi Medical University Cancer Hospital, Nanning, Guangxi, China
| | - Dewen Mao
- Department of Live Disease, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China
| | - Yinjie Meng
- Department of Live Disease, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China
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9
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Zhong S, Zhang T, Tang L, Li Y. Cytokines and Chemokines in HBV Infection. Front Mol Biosci 2021; 8:805625. [PMID: 34926586 PMCID: PMC8674621 DOI: 10.3389/fmolb.2021.805625] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 11/15/2021] [Indexed: 12/21/2022] Open
Abstract
Chronic hepatitis B virus (HBV) infection remains a leading cause of hepatic inflammation and damage. The pathogenesis of chronic hepatitis B (CHB) infection is predominantly mediated by persistent intrahepatic immunopathology. With the characterization of unique anatomical and immunological structure, the liver is also deemed an immunological organ, which gives rise to massive cytokines and chemokines under pathogenesis conditions, having significant implications for the progression of HBV infection. The intrahepatic innate immune system is responsible for the formidable source of cytokines and chemokines, with the latter also derived from hepatic parenchymal cells. In addition, systemic cytokines and chemokines are disturbed along with the disease course. Since HBV is a stealth virus, persistent exposure to HBV-related antigens confers to immune exhaustion, whereby regulatory cells are recruited by intrahepatic chemokines and cytokines, including interleukin-10 and transforming growth factor β, are involved in such series of causal events. Although the considerable value of two types of available approved treatment, interferons and nucleos(t)ide analogues, effectively suppress HBV replication, neither of them is sufficient for optimal restoration of the immunological attrition state to win the battle of the functional or virological cure of CHB infection. Notably, cytokines and chemokines play a crucial role in regulating the immune response. They exert effects by directly acting on HBV or indirectly manipulating target immune cells. As such, specific cytokines and chemokines, with a potential possibility to serve as novel immunological interventions, combined with those that target the virus itself, seem to be promising prospects in curative CHB infection. Here, we systematically review the recent literature that elucidates cytokine and chemokine-mediated pathogenesis and immune exhaustion of HBV infection and their dynamics triggered by current mainstream anti-HBV therapy. The predictive value of disease progression or control and the immunotherapies target of specific major cytokines and chemokines in CHB infection will also be delineated.
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Affiliation(s)
- Shihong Zhong
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Tianling Zhang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Libo Tang
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yongyin Li
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
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10
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Khorram FS, Mehdipour A, Moghadam-Ahmadi A, Farahmand H, Askari A, Moosavi SM, Shabanizadeh A, Parsi M, Arababadi MK. Brain magnetic resonance imaging without contrast significantly increased serum levels of IL-6, but not IL-10, IL-17A and TGF-β. Brain Inj 2021; 35:1451-1456. [PMID: 34495795 DOI: 10.1080/02699052.2021.1972446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Introduction: Magnetic Resonance Imaging (MRI) is a non-invasive imaging modality. However, the effects of MRI on the immune system in the in vivo conditions are yet to be clarified. In this study we explored the effects of routine brain MRI on the protein and mRNA peripheral blood levels of interleukin-6 (IL-6), IL-10, IL-17A and transforming growth factor-beta (TGF-β).Material and methods: 40 subjects, who referred for brain MRI, were entered for evaluating effects of routine brain MRI on the protein and mRNA peripheral blood levels of IL-6, IL-10, IL-17A and TGF-β. Accordingly, peripheral blood were collected before and 3 hours after MRI from the participants. Protein levels of the cytokines were evaluated using ELISA. Also, mRNA levels were analyzed using Real-Time PCR techniques.Results: Brain MRI without contrast led to an increase in protein levels of IL-6 in the peripheral serum, but did not change protein and mRNA levels of IL-10, IL-17A and TGF-β. IL-6 mRNA levels after MRI were higher in the participants with mild anxiety compared to those without anxiety.Conclusion: brain MRI without contrast can induce secretion of IL-6 and may be associated with its functions, such as development of plasma cells or induction of inflammation.
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Affiliation(s)
- Faezeh-Sadat Khorram
- Geriatric Care Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Radiology, Faculty of Paramedicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Ali Mehdipour
- Geriatric Care Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Radiology, Faculty of Paramedicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Amir Moghadam-Ahmadi
- Non-Communicable Diseases Research Center. Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department Neurology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Habib Farahmand
- Non-Communicable Diseases Research Center. Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department Radiology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Azadeh Askari
- Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Laboratory Sciences, Faculty of Paramedicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Seyed Mohsen Moosavi
- Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Laboratory, Faculty of Paramedicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Ahmad Shabanizadeh
- Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Anatomy, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Masoumeh Parsi
- Geriatric Care Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Radiology, Faculty of Paramedicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Mohammad Kazemi Arababadi
- Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Laboratory Sciences, Faculty of Paramedicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
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Local and systemic gene expression levels of IL-10, IL-17 and TGF-β in active ocular toxoplasmosis in humans. Cytokine 2021; 146:155643. [PMID: 34332275 DOI: 10.1016/j.cyto.2021.155643] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 07/05/2021] [Accepted: 07/06/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND To compare mRNA expression of interleukin 10 (IL-10), interleukin 17 (IL-17) and Transforming Growth Factor-β (TGF-β) in aqueous humor (AH) and peripheral blood mononuclear cells (PBMCs) in human ocular toxoplasmosis (OT) and controls. METHOD RNA isolation, cDNA synthesis and real-time polymerase chain reaction were performed on AH sediments and PBMCs of 16 patients with active OT and 21 controls at the Khatam-al-Anbia Eye Hospital, Iran. For comparison, Mann Whitney U test was used at a discrimination level of p < 0.05. Pearson and Spearman rank correlation test were applied for correlation with clinical parameters. RESULTS The expression for IL-10 and IL-17 in the AH was 3.7- and 88.0-fold higher in OT than in controls (P = 0.04 and P = 0.03, respectively) whereas that of TGF-β was 7.7-fold lower (P < 0.001). The expression levels for these cytokines in PBMC followed a similar pattern (IL-10 13.8-fold down-regulated (P = 0.001), IL-17 with 1.9-fold insignificantly upregulated (p = 0.43), TGF-β 452.8-fold down-regulated (P = 0.002). Compared to PBMC, IL-10 coding mRNA was 1876-fold higher in the almost cell-free AH in OT (39.2-fold in controls), IL-17 coding mRNA was 9.4-fold higher (17.7-fold down-regulated in controls), and that coding for TGF-β 207-fold higher in OT (7x105-fold in controls). The expression for IL-10, IL-17 and TGF-β in AH thus followed an opposite pattern compared to that in PBMC. CONCLUSION OT induces a highly-specific local immunoregulatory process as evidenced by an intraocular up-regulation of IL-10 and down-regulation of TGF-β mRNA. This could indicate an attempt to prevent unnecessary tissue damage which is in line with a moderate local mRNA up-regulation for IL-17 which seems sufficient to control parasite proliferation. That this regulation is opposite to that in PBMC may be linked to intraocular immune deviation in the course of disease.
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12
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Yao J, Lin C, Jiang J, Zhang X, Li F, Liu T, Diao H. lncRNA-HEIM Facilitated Liver Fibrosis by Up-Regulating TGF- β Expression in Long-Term Outcome of Chronic Hepatitis B. Front Immunol 2021; 12:666370. [PMID: 34168644 PMCID: PMC8217658 DOI: 10.3389/fimmu.2021.666370] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 05/18/2021] [Indexed: 12/26/2022] Open
Abstract
Background Chronic liver fibrosis is an inevitable stage for the development of patients with chronic hepatitis B (CHB). However, anti-fibrotic therapies have been unsuccessful so far. The biological functions and molecular mechanisms of long non-coding RNAs (lncRNAs) in the host immune system during chronic hepatitis B virus (HBV) infection, especially in fibrosis, are still largely unknown. Method The total RNA of peripheral blood mononuclear cells (PBMCs) from asymptomatic carriers (ASCs) or CHB receiving at least 8 years of anti-viral treatments was analyzed using Arraystar microarray and validated via quantitative real-time PCR (qRT-PCR). Correlation analysis was conducted based on correlation coefficients, Clusterprofile, and RNA Interactome Database (RAID). The functions of lncRNA in monocytes were determined via loss-of-function RNAi or gain-of-function lentivirus assays. The expression levels of mRNAs or proteins were evaluated using qRT-PCR, western blotting assay, or enzyme linked immunosorbent assays (ELISA). Results A total of 1,042 mRNA transcripts (630 up-regulated and 412 down-regulated) were identified being differentially expressed between ASC and CHB patients. Through enrichment analysis we focused on the transforming growth factor beta (TGF-β) signaling pathway and validated their expression in a larger cohort. Moreover, we found that lncRNA ENST00000519726 (lncRNA-HEIM) was highly expressed in monocytes and further up-regulated upon HBV infection. LncRNA-HEIM played an important role in CHB patients with long-term antiviral treatments, and its elevated expression was remarkably correlated with the TGF-β signaling pathway, especially with the two members namely TGF-β and SMAD4. Furthermore, altering the endogenous lncRNA-HEIM level in monocytes significantly affected the production of TGF-β, as well as the fibrosis of hepatic stellate cells by affecting the expression of collagen I and α-smooth muscle actin (α-SMA). Conclusion These findings not only added knowledge to the understanding of the roles of which lncRNA-HEIM played in the activation of HSCs in CHB patients with long-term medication, but also provided a promising therapeutic target in the future treatment for liver fibrosis.
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Affiliation(s)
- Jian Yao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chenhong Lin
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jingjing Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xujun Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Fengxia Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Tianxing Liu
- Department of Biological Sciences, University of Toronto, Toronto, ON, Canada
| | - Hongyan Diao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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13
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Aghbash PS, Hemmat N, Nahand JS, Shamekh A, Memar MY, Babaei A, Baghi HB. The role of Th17 cells in viral infections. Int Immunopharmacol 2021; 91:107331. [PMID: 33418239 DOI: 10.1016/j.intimp.2020.107331] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 12/19/2020] [Accepted: 12/20/2020] [Indexed: 02/07/2023]
Abstract
The present review provides an overview of recent advances regarding the function of Th17 cells and their produced cytokines in the progression of viral diseases. Viral infections alone do not lead to virus-induced malignancies, as both genetic and host safety factors are also involved in the occurrence of malignancies. Acquired immune responses, through the differentiation of Th17 cells, form the novel components of the Th17 cell pathway when reacting with viral infections all the way from the beginning to its final stages. As a result, instead of inducing the right immune responses, these events lead to the suppression of the immune system. In fact, the responses from Th17 cells during persistent viral infections causes chronic inflammation through the production of IL-17 and other cytokines which provide a favorable environment for tumor growth and its development. Additionally, during the past decade, these cells have been understood to be involved in tumor progression and metastasis. However, further research is required to understand Th17 cells' immune mechanisms in the vast variety of viral diseases. This review aims to determine the roles and effects of the immune system, especially Th17 cells, in the progression of viral diseases; which can be highly beneficial for the diagnosis and treatment of these infections.
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Affiliation(s)
- Parisa Shiri Aghbash
- Immunology Research Center, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran; Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran
| | - Nima Hemmat
- Immunology Research Center, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran; Drug Applied Research Centre, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran
| | - Javid Sadri Nahand
- Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, ZIP Code 14155 Tehran, Iran; Student Research Committee, Iran University of Medical Sciences, ZIP Code 14155 Tehran, Iran
| | - Ali Shamekh
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran
| | - Mohammad Yousef Memar
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran
| | - Abouzar Babaei
- Department of Virology, Faculty of Medicine, Tarbiat Modares University, ZIP Code 14155 Tehran, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Center, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran; Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran; Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, ZIP Code 15731 Tabriz, Iran.
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Ehsani V, Mortazavi M, Ghorban K, Dadmanesh M, Bahramabadi R, Rezayati MT, Javadi-Moghadam E, Rezaei Z, Sabzali Z, Fatemi I, Sheikh Fathollahi M, Kazemi Arababadi M. Role of maternal interleukin-8 (IL-8) in normal-term birth in the human. Reprod Fertil Dev 2020; 31:1049-1056. [PMID: 30922438 DOI: 10.1071/rd18361] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Accepted: 01/07/2019] [Indexed: 12/17/2022] Open
Abstract
Cytokines are the main factors involved in the normal functions of the placenta and delivery process. The aim of this project was to compare serum levels of interleukin-8 (IL-8), IL-6, tumour necrosis factor α (TNF-α) and transforming growth factor β (TGF-β) in term and prolonged-pregnancy mothers and their neonates. This study was performed on 240 participants including 60 term and prolonged-pregnancy neonates and their corresponding mothers. Serum levels of IL-8, IL-6, TNF-α and TGF-β were evaluated by the enzyme-linked immunosorbent assay technique. The results revealed that IL-8 serum levels were significantly lower in the prolonged-pregnancy mothers and their neonates when compared with term mothers and their neonates. Data analysis also revealed a negative correlation between TGF-β and age of prolonged-pregnancy mothers. A poor positive correlation between IL-6 and head circumference of term neonates was also observed. IL-8 may play crucial roles in the process of on-time delivery and age may significantly affect TGF-β production in prolonged-pregnancy mothers. Pro-inflammatory cytokines, such as IL-6, can also be considered as main factors involved in fetal growth.
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Affiliation(s)
- Vahid Ehsani
- Immunology of Infectious Diseases Research Centre, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran
| | - Maryam Mortazavi
- Immunology of Infectious Diseases Research Centre, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran; and Department of Gynaecology and Obstetrics, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran; and Corresponding author.
| | - Khodayar Ghorban
- Department of Immunology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Maryam Dadmanesh
- Department of Infectious Diseases, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Reza Bahramabadi
- Immunology of Infectious Diseases Research Centre, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran; and Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, 7616913555, Iran
| | - Mohammad-Taghi Rezayati
- Immunology of Infectious Diseases Research Centre, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran
| | - Esmat Javadi-Moghadam
- Department of Gynaecology and Obstetrics, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran
| | - Zahra Rezaei
- Department of Gynaecology and Obstetrics, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran
| | - Zahra Sabzali
- Department of Gynaecology and Obstetrics, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran
| | - Iman Fatemi
- Physiology-Pharmacology Research Centre, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran; and Department of Physiology and Pharmacology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran
| | - Mahmood Sheikh Fathollahi
- Immunology of Infectious Diseases Research Centre, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran; and Department of Biostatistics, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran
| | - Mohammad Kazemi Arababadi
- Immunology of Infectious Diseases Research Centre, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran; and Department of Laboratory Medicine, Faculty of Paramedicine, Rafsanjan University of Medical Sciences, Rafsanjan, 7719617996, Iran
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Detection of Hepatitis B Surface Antigen among Febrile Patients in Ankpa, Kogi State, Nigeria. J Trop Med 2020; 2020:5136785. [PMID: 32095141 PMCID: PMC7036110 DOI: 10.1155/2020/5136785] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 12/12/2019] [Accepted: 01/20/2020] [Indexed: 12/15/2022] Open
Abstract
Background Hepatitis B virus (HBV) infection has become a significant public health problem in developing countries, and the high rate of morbidity and mortality from acute and chronic infections is worrisome. Therefore, this study determined the prevalence of HBV and associated risk factors in Ankpa, Kogi State, Nigeria. Materials and Methods. Sera randomly collected from 200 participants in three public hospitals in Ankpa were screened for HBsAg using commercially available HBsAg rapid test kit (Swe-Care (R), China). Structured questionnaires were used to obtain sociodemographic details and history of exposure to risk factors. Results Seventeen (8.5%) of the 200 patients were positive for HBsAg. Males had higher prevalence (10.89%) than females (6.06%). The age group with the highest rate of infection was 24–44 years. Patient's occupation and marital status were significantly higher in relation to HBsAg seropositivity. Risks of HBV infection in Ankpa are sharing of sharp objects (OR = 11.62, 95% CI, 3.59–37.59), multiple sexual partners (OR = 3.39, 95% CI, 1.23–9.38), blood transfusion (OR = 13.74, 95% CI, 4.22–44.71), surgeries (OR = 3.02, 95% CI, 1.03–8.83), alcoholism (OR = 6.94, 95% CI, 2.32–20.75), mouth-to-mouth kissing (p=0.001), and contact with HBV patient (OR = 4.14, 95% CI, 1.01–17.06). People without prior knowledge of HBV infection were more infected. Conclusion This study reaffirms the endemicity of HBV in a part of sub-Saharan African country. Public health practitioners should focus attention on apparently healthy patients in developing countries. We suggest inclusion of HBsAg screening for patients coming for routine hospital care.
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Omatola CA, Okolo MLO, Adaji DM, Mofolorunsho CK, Abraham Oyiguh J, Zige DV, Akpala NS, Ocholi Samson S. Coinfection of Human Immunodeficiency Virus-Infected Patients with Hepatitis B Virus in Lokoja, North Central Nigeria. Viral Immunol 2020; 33:391-395. [PMID: 32031904 DOI: 10.1089/vim.2019.0157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Globally, coinfection of human immunodeficiency virus (HIV) patients with Hepatitis B Virus (HBV) is associated with an accelerated progression of HIV disease and higher mortality resulting from complications of liver-related disease. Despite the public health importance, data are lacking on this subject in the study area. Therefore, we evaluated the prevalence and risk factors for HIV/HBV coinfection among HIV patients accessing antiretroviral treatment in Lokoja, Nigeria. In a cross-sectional study, sera from randomly selected 200 consenting HIV patients were screened for hepatitis B surface antigen (HBsAg) using The Commercial Rapid Immunoassay Test Kit. Demographic variables and putative risk factors of HBV transmission were obtained using structured questionnaire. HBsAg prevalence was 8.0% in the sampled group with higher seropositivity rate in the age group, 40-49 years, followed by those 20-29 years of age, whereas the other age groups had zero positivity rates each. The difference between seroprevalence rates in relation to patients' age and sex was not statistically significant (p > 0.05). Patients with no formal education, who were married and were housewives, had higher rates of HBV infection compared with others in the group. Although not statistically significant (p > 0.05), the likelihood of exposure to HBV was higher among patients who were engaged in multiple sexual behaviors, alcoholism, smoking, sharing of sharps, ear piercing, and had history of blood transfusion. Conclusively, HIV/HBV coinfection rate in our study is comparable to other localities and thus, affirm the endemicity in the study area. The need to strengthen health education of the masses to desist from risky behaviors is recommended to reduce the morbidity and mortality arising from HIV/HBV comorbidity.
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Affiliation(s)
| | | | - David Moses Adaji
- Department of Microbiology, Kogi State University, Anyigba, Nigeria.,Center for Space Transport and Proportion, Lagos State University, Epe Lagos, Nigeria
| | | | | | - Douye Victor Zige
- Department of Microbiology, Federal University Otuoke, Otuoke, Nigeria
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17
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Zheng W, Yao M, Fang M, Pan L, Wang L, Yang J, Dong Z, Yao D. Oncogenic Wnt3a: A Candidate Specific Marker and Novel Molecular Target for Hepatocellular Carcinoma. J Cancer 2019; 10:5862-5873. [PMID: 31737122 PMCID: PMC6843874 DOI: 10.7150/jca.31599] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 08/20/2019] [Indexed: 12/22/2022] Open
Abstract
Background and aim: It is of the utmost importance for the specific diagnosis and effective therapy of hepatocellular carcinoma (HCC). Abnormality of oncogenic Wingless-type MMTV integration site family member 3a (Wnt3a) has been associated with progression of HCC. In this study, we aimed to evaluate Wnt3a as a novel biomarker and target for HCC. Methods: Circulating Wnt3a levels were quantitatively detected in a cohort of chronic liver diseases by an enzyme-linked immune-absorbent assay (ELISA). Hepatic Wnt3a expression in HCC and para-cancerous tissues was analyzed by immunohistochemistry. Prognostic value of Wnt3a for HCC was discovered in the cohort from the Cancer Genome Atlas (TCGA). Dynamic alterations of Wnt3a levels were detected in the hepatocarcinogenesis model induced by 2-acetylaminofluorene. Effects of Wnt3a on biological behaviors were evaluated in vitro and in vivo based on Crispr/Cas9. Results: Up-regulated Wnt3a levels were observed in serum of HCC patients with high specificity and sensitivity for HCC diagnosis. Combination of Wnt3a and AFP could improve sensitivity to 93.9% in serological detection. In addition, Wnt3a expression in HCC tissues was significantly higher than that in para-cancerous tissues. The cohort of TCGA demonstrated that high Wnt3a expression led to a poor survival of HCC patients, especially in cases at advanced stages. Furthermore, the hepatocarcinogenesis model showed that Wnt3a dynamically increased in the development of HCC. Functionally, silencing Wnt3a by Crispr/Cas9 suppressed the proliferation, colony formation, induced cell cycle arrest of HCC cells by de-activating Wnt/β-catenin pathway in vitro, and inhibited xenograft tumor growth in vivo. Conclusions: Oncogenic Wnt3a could be considered as a candidate biomarker and novel target for HCC.
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Affiliation(s)
- Wenjie Zheng
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Min Yao
- Department of Medical Immunology, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Miao Fang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Liuhong Pan
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Li Wang
- Department of Medical Informatics, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Junling Yang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Zhizhen Dong
- Department of Diagnostics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
| | - Dengfu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
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Yuan B, Liu J, Cao J, Yu Y, Zhang H, Wang F, Zhu Y, Xiao M, Liu S, Ye Y, Ma L, Xu D, Xu N, Li Y, Zhao B, Xu P, Jin J, Xu J, Chen X, Shen L, Lin X, Feng X. PTPN3 acts as a tumor suppressor and boosts TGF-β signaling independent of its phosphatase activity. EMBO J 2019; 38:e99945. [PMID: 31304624 PMCID: PMC6627230 DOI: 10.15252/embj.201899945] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 03/14/2019] [Accepted: 03/28/2019] [Indexed: 12/22/2022] Open
Abstract
TGF-β controls a variety of cellular functions during development. Abnormal TGF-β responses are commonly found in human diseases such as cancer, suggesting that TGF-β signaling must be tightly regulated. Here, we report that protein tyrosine phosphatase non-receptor 3 (PTPN3) profoundly potentiates TGF-β signaling independent of its phosphatase activity. PTPN3 stabilizes TGF-β type I receptor (TβRI) through attenuating the interaction between Smurf2 and TβRI. Consequently, PTPN3 facilitates TGF-β-induced R-Smad phosphorylation, transcriptional responses, and subsequent physiological responses. Importantly, the leucine-to-arginine substitution at amino acid residue 232 (L232R) of PTPN3, a frequent mutation found in intrahepatic cholangiocarcinoma (ICC), disables its role in enhancing TGF-β signaling and abolishes its tumor-suppressive function. Our findings have revealed a vital role of PTPN3 in regulating TGF-β signaling during normal physiology and pathogenesis.
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Affiliation(s)
- Bo Yuan
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Jinquan Liu
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Jin Cao
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Yi Yu
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Hanchenxi Zhang
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Fei Wang
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Yezhang Zhu
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Mu Xiao
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Sisi Liu
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Youqiong Ye
- Department of Biochemistry and Molecular BiologyUniversity of Texas Health Science CenterHoustonTXUSA
| | - Le Ma
- Department of Molecular & Cellular BiologyBaylor College of MedicineHoustonTXUSA
| | - Dewei Xu
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Ningyi Xu
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Yi Li
- Department of Molecular & Cellular BiologyBaylor College of MedicineHoustonTXUSA
| | - Bin Zhao
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Pinglong Xu
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Jianping Jin
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Jianming Xu
- Department of Molecular & Cellular BiologyBaylor College of MedicineHoustonTXUSA
| | - Xi Chen
- Department of Biochemistry and Molecular BiologyUniversity of Texas Health Science CenterHoustonTXUSA
| | - Li Shen
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
| | - Xia Lin
- Michael DeBakey Department of SurgeryBaylor College of MedicineHoustonTXUSA
| | - Xin‐Hua Feng
- The MOE Key Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhouZhejiangChina
- Department of Molecular & Cellular BiologyBaylor College of MedicineHoustonTXUSA
- Michael DeBakey Department of SurgeryBaylor College of MedicineHoustonTXUSA
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Omatola CA, Idofe J, Okolo MLO, Adejo PO, Maina MM, Oyiguh JA. Seroprevalence of HBV among people living with HIV in Anyigba, Kogi State, Nigeria. Afr Health Sci 2019; 19:1938-1946. [PMID: 31656477 PMCID: PMC6794505 DOI: 10.4314/ahs.v19i2.17] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background Co-infection of HBV with HIV is associated with significant morbidity and mortality globally. In spite of increasing reports of HIV/HBV co-morbidities in Nigeria, little or no data exists on this subject in Anyigba. Therefore, we determined the prevalence of hepatitis B surface antigenemia among HIV positive patients on anti-retroviral treatment programme in Anyigba, Kogi State, North-Central Nigeria. Methods Sera samples obtained from 200 consented HIV patients were screened for HBsAg using the commercial rapid test membrane-based qualitative immunoassay. A structured questionnaire was used to collect information on patients' demographic variables and probable risk factors for HBV transmission. Results Overall, 3.5% of HIV patients were seropositive to HBsAg and the difference between seroprevalence rates and patients' age as well as gender was not statistically significant (p>0.05). There was significant difference between patients' demographic variables such as marital status (p=0.013) and educational level (p=0.004) and HBsAg seropositivity. Patients with a history of surgical applications (p=0.01) and who indulged in alcoholism (p=0.03) significantly had higher rates of concomitant HIV/HBV infection in the study area. Conclusion Our findings underscore the importance of routine screening for HBV in the HIV infected populations especially in developing countries where the infection is endemic. We advocate for public enlightenment programmes on routes of virus acquisitions with a view to reduce the morbidity and mortality associated HIV/HBV co-infection.
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Dadmanesh M, Ranjbar MM, Ghorban K. Inflammasomes and their roles in the pathogenesis of viral hepatitis and their related complications: An updated systematic review. Immunol Lett 2019; 208:11-18. [PMID: 30831142 PMCID: PMC7112799 DOI: 10.1016/j.imlet.2019.03.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 02/26/2019] [Accepted: 03/01/2019] [Indexed: 02/06/2023]
Abstract
Inflammasomes are a set of innate receptors which are the responsible molecules for activation of pro-interleukin (IL)-1β and IL-18 and induction of inflammation. Due to the key roles of the inflammasomes in the induction of inflammation, it has been hypothesized that the molecules may be the main parts of immune responses against viral infections and the tissue damage. Because some cases of viral hepatitis infections, including hepatitis B and C, are diagnosed as chronic and may be associated with various complications such as liver cirrhosis and hepatocellular carcinoma (HCC), several studies focused on the roles played by the inflammation on the pathogenesis of viral hepatitis. Based on the roles played by inflammasomes in induction of inflammation, it has been hypothesized that inflammasomes may be the main parts of the puzzle of the viral hepatitis complications. This article reviews the roles of the inflammasomes in the pathogenesis of hepatitis B and C viral infections and their complications, liver cirrhosis, and HCC.
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Affiliation(s)
- Maryam Dadmanesh
- Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran; Department of Infectious Diseases, Medical School, Aja University of Medical Sciences, Tehran, Iran
| | - Mohammad Mehdi Ranjbar
- Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.
| | - Khodayar Ghorban
- Infectious Diseases Research Center, Aja University of Medical Sciences, Tehran, Iran; Department of Immunology, Medical School, Aja University of Medical Sciences, Tehran, Iran.
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Shata MTM, Abdel-Hameed EA, Rouster SD, Yu L, Liang M, Song E, Esser MT, Shire N, Sherman KE. HBV and HIV/HBV Infected Patients Have Distinct Immune Exhaustion and Apoptotic Serum Biomarker Profiles. Pathog Immun 2019; 4:39-65. [PMID: 30815625 PMCID: PMC6388707 DOI: 10.20411/pai.v4i1.267] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background: Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to their shared routes of transmission, approximately 10% of HIV-infected patients worldwide are chronically coinfected with HBV. Additionally, liver disease has become a major cause of morbidity and mortality in HBV/HIV coinfected patients due to prolonged survival with the success of antiretroviral therapy. The relationship between immune exhaustion markers (PD-1/PD-L1) and apoptotic markers such as Fas/FasL, TGFβ1, TNF-α, and Th1/Th2 cytokines are not clearly delineated in HBV/HIV coinfection. Methods: Levels of soluble Fas/FasL, TGFβ1, TNF-α, and sPD-1/sPD-L1 as well as Th1 and Th2 cytokines were evaluated in the sera of HBV-monoinfected (n = 30) and HBV/HIV-coinfected (n = 15) patients and compared to levels in healthy controls (n = 20). Results: HBV-monoinfected patients had significantly lower levels of the anti-inflammatory cytokine IL-4 (P < 0.05) and higher levels of apoptotic markers sFas, sFasL, and TGFβ-1 (P < 0.001) compared to healthy controls. Coinfection with HIV was associated with higher levels of sFas, TNF-α, and sPD-L1 (P < 0.005), and higher levels of the pro-inflammatory cytokines IL-6, IL-8, and IL-12p70 (P < 0.05) compared to healthy controls. Patients with HBV infection had a unique biomarker clustering profile comprised of IFN-γ, IL12p70, IL-10, IL-6, and TNF-α that was distinct from the profile of the healthy controls, and the unique HIV/HBV profile comprised GM-CSF, IL-4, IL-2, IFN-γ, IL12p70, IL-7, IL-10, and IL-1β. In HBV monoinfection a significant correlation between sFasL and PD1(r = 0.46, P = < 0.05) and between sFas and PDL1 (r = 0.48, P = <0.01) was observed. Conclusion: HBV-infected and HBV/HIV-coinfected patients have unique apoptosis and inflammatory biomarker profiles that distinguish them from each other and healthy controls. The utilization of those unique biomarker profiles for monitoring disease progression or identifying individuals who may benefit from novel immunotherapies such as anti-PD-L1 or anti-PD-1 checkpoint inhibitors appears promising and warrants further investigation.
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Affiliation(s)
| | | | - Susan D Rouster
- Internal medicine; University of Cincinnati; Cincinnati, Ohio
| | - Li Yu
- MedImmune; Gaithersburg, Maryland
| | - Meina Liang
- MedImmune; 121 Oyster Point Boulevard; South San Francisco, California
| | - Esther Song
- MedImmune; 121 Oyster Point Boulevard; South San Francisco, California
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22
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Asadikaram G, Akbari H, Safi Z, Shadkam M, Khaksari M, Shahrokhi N, Najafipour H, Sanjari M, Arababadi MK. Downregulation of IL-22 can be considered as a risk factor for onset of type 2 diabetes. J Cell Biochem 2018; 119:9254-9260. [PMID: 29953655 DOI: 10.1002/jcb.27194] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Accepted: 05/24/2018] [Indexed: 12/16/2022]
Abstract
There is some controversy as for the roles played by tumor growth factor-β (TGF-β), interleukin-1β (IL-1β), and IL-22 in the onset process of type 2 diabetes (T2D). The main aim of this project was to examine serum levels of TGF-β, IL-1β, and IL-22 in the new cases and long period T2D patients as well as healthy controls. In this study, 115 new T2D patient cases (group 1), 434 T2D patients who have suffered from the disease more than 2 years (group 2), and 104 healthy controls have been selected from 6240 (3619 females) patients who were under study population from Kerman Coronary Artery Disease Risk Factor Study. Serum levels of TGF-β, IL-1β, and IL-22 have been evaluated using commercial kits. Serum levels of TGF-β and IL-1β significantly increased, while IL-22 decreased in 2 groups in comparison to healthy controls. Serum levels of IL-22, but not TGF-β and IL-1β, were significantly decreased in group 1 in comparison to healthy controls. There were no significant differences between groups 1 and 2 as for the cytokine levels. Serum levels of IL-22 increased in the females in group 2 when compared to females in group 1. It appears that TGF-β and IL-1β participate in the induction of inflammation after establishment of T2D, while decrease in IL-22 may be considered as a key factor for onset of the disease. Gender can also be considered as the main risk factor for variation in cytokine levels.
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Affiliation(s)
- Gholamreza Asadikaram
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
- Department of Biochemistry, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Hamed Akbari
- Department of Biochemistry, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Zohreh Safi
- Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Mitra Shadkam
- Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Khaksari
- Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
- Department of Physiology, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Nader Shahrokhi
- Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
- Department of Physiology, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Hamid Najafipour
- Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
- Department of Physiology, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mojgan Sanjari
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Kazemi Arababadi
- Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
- Department of Immunology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
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23
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Asadikaram G, Ram M, Izadi A, Sheikh Fathollahi M, Nematollahi MH, Najafipour H, Shahoozehi B, Mirhoseini M, Masoumi M, Shahrokhi N, Arababadi MK. The study of the serum level of IL-4, TGF-β, IFN-γ, and IL-6 in overweight patients with and without diabetes mellitus and hypertension. J Cell Biochem 2018; 120:4147-4157. [PMID: 30260038 DOI: 10.1002/jcb.27700] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 08/27/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND Obesity increases the risk of diabetes mellitus (DM) and hypertension. We aimed to analyze the serum levels of cytokines that have relevance to the pathologies including, interleukin-4 (IL-4), transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), and IL-6 cytokines of overweight men with DM and/or hypertension. METHODS The study collected serum from 164 men. The sample population contained, 54 overweight men without DM or hypertension (control [CTL] group), 36 men with both DM and hypertension (DH group), 20 men with DM but no hypertension (D group), and 54 had hypertension without DM (H). RESULTS The main results showed that the concentration of IFN-γ in the DH group was significantly higher than the D, H, and CTL groups, IL-6 in DH and D groups was significantly lower than the CTL group. The serum level of TGF-β and IL-4 cytokines did not show any significant differences across the four groups. Serum levels of IL-6 were also significantly lower in untreated patients in D group than controls and in DH when compared with H groups. CONCLUSION In conclusion, it appears that the proinflammatory and anti-inflammatory cytokines either play a significant role in the pathogenesis of hypertension and DM or serve as markers for these pathologies. Accordingly, increased serum levels of IFN-γ may participate in the pathogenesis of hypertension in the diabetic patients and decreased IL-6 is associated with type 2 DM.
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Affiliation(s)
- Gholamreza Asadikaram
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.,Department of Biochemistry, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Maryam Ram
- Department of Biochemistry, Taft Payam Noor University, Yazd, Iran
| | - Alireza Izadi
- Department of Medical Mycology and Parasitology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mahmood Sheikh Fathollahi
- Department of Epidemiology and Biostatistics, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Mohammad Hadi Nematollahi
- Department of Biochemistry, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Hamid Najafipour
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Bidollah Shahoozehi
- Department of Biochemistry, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Mohammad Masoumi
- Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Nader Shahrokhi
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Kazemi Arababadi
- Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Immunology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Kerman, Iran
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24
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Zhao D, Jiang X, Xu Y, Yang H, Gao D, Li X, Gao L, Ma C, Liang X. Decreased Siglec-9 Expression on Natural Killer Cell Subset Associated With Persistent HBV Replication. Front Immunol 2018; 9:1124. [PMID: 29899741 PMCID: PMC5988867 DOI: 10.3389/fimmu.2018.01124] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Accepted: 05/03/2018] [Indexed: 12/23/2022] Open
Abstract
Siglec-9 is an MHC-independent inhibitory receptor selectively expressed on CD56dim NK cells. Its role in infection diseases has not been investigated yet. Here, we studied the potential regulatory roles of NK Siglec-9 in the pathogenesis of chronic hepatitis B (CHB) infection. Flow cytometry evaluated the expression of Siglec-9 and other receptors on peripheral NK cells. Immunofluorescence staining was used to detect Siglec-9 ligands on liver biopsy tissues and cultured hepatocyte cell lines. Siglec-9 blocking assay was carried out and cytokine synthesis and CD107a degranulation was detected by flow cytometry. Compared to healthy donors, CHB patients had decreased Siglec-9+ NK cells, which reversely correlated with serum hepatitis B e antigen and HBV DNA titer. Siglec-9 expression on NK cells from patients achieving sustained virological response recovered to the level of normal donors. Neutralization of Siglec-9 restored cytokine synthesis and degranulation of NK cells from CHB patients. Immunofluorescence staining showed increased expression of Siglec-9 ligands in liver biopsy tissues from CHB patients and in hepatocyte cell lines infected with HBV or stimulated with inflammatory cytokines (IL-6 or TGF-β). These findings identify Siglec-9 as a negative regulator for NK cells contributing to HBV persistence and the intervention of Siglec-9 signaling might be of potentially translational significance.
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Affiliation(s)
- Di Zhao
- Key Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, Shandong University School of Medicine, Jinan, China.,Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, China
| | - Xuemei Jiang
- Key Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, Shandong University School of Medicine, Jinan, China.,Department of Hepatic Diseases, Jinan Infectious Disease Hospital, Jinan, China
| | - Yong Xu
- Key Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, Shandong University School of Medicine, Jinan, China
| | - Huimin Yang
- Department of Nephrology, Qilu Hospital, Shandong University, Jinan, China
| | - Dongni Gao
- Key Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, Shandong University School of Medicine, Jinan, China
| | - Xueen Li
- Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, China
| | - Lifen Gao
- Key Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, Shandong University School of Medicine, Jinan, China
| | - Chunhong Ma
- Key Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, Shandong University School of Medicine, Jinan, China
| | - Xiaohong Liang
- Key Laboratory for Experimental Teratology of Ministry of Education, Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, Shandong University School of Medicine, Jinan, China
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25
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Bahramabadi R, Fathollahi MS, Hashemi SM, Arababadi AS, Arababadi MS, Yousefi-Daredor H, Bidaki R, Khaleghinia M, Bakhshi MH, Yousefpoor Y, Torbaghan YE, Arababadi MK. Serum Levels of IL-6, IL-8, TNF-α, and TGF-β in Chronic HBV-Infected Patients: Effect of Depression and Anxiety. Lab Med 2018; 49:41-46. [PMID: 29237050 DOI: 10.1093/labmed/lmx064] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Objective To assess the effects of depression and anxiety on serum cytokine levels in patients with chronic hepatitis B (CHB) infection. Methods In this cross-sectional study, 60 healthy control individuals and 60 patients with CHB participated after filling out standard questionnaires. We examined their serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and TGF-β levels using enzyme-linked immunosorbent assay (ELISA) techniques. Results In patients with CHB compared with healthy controls, serum levels of IL-8 were significantly increased, whereas IL-6 and TGF-β levels were significantly decreased. Serum levels of TGF-β were significantly decreased in the patients with CHB who had mild depression, compared with patients with CHB without depression and with moderate and severe depression. Conclusions Downregulation of IL-8 and TGF-β, respectively, is a corresponding mechanism for induction of chronic inflammation in patients with CHB. Depression also seems to induce inflammation via downregulation of TGF-β in these patients.
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Affiliation(s)
- Reza Bahramabadi
- Immunology of Infectious Diseases Research Center, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Immunology, Faculty of Medicine, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Mahmood Sheikh Fathollahi
- Immunology of Infectious Diseases Research Center, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Epidemiology and Biostatistics, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | | | - Amin Safari Arababadi
- Immunology of Infectious Diseases Research Center, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Minoo Safari Arababadi
- Immunology of Infectious Diseases Research Center, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Hassan Yousefi-Daredor
- Immunology of Infectious Diseases Research Center, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Reza Bidaki
- Research Center of Addiction and Behavioral Sciences, Shahid Sadoughi University of Medical Science, Yazd, Iran.,Diabetes Research Center, Shahid Sadoughi University of Medical Science, Yazd, Iran
| | - Mehdi Khaleghinia
- Department of Infectious Diseases, Medical School, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Hossein Bakhshi
- Immunology of Infectious Diseases Research Center, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Yaser Yousefpoor
- Khalil Abad Health Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Mohammad Kazemi Arababadi
- Immunology of Infectious Diseases Research Center, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Immunology, Faculty of Medicine, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
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26
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Eskandari E, Metanat M, Pahlevani E, Nakhzari-Khodakheir T. Association between TGFβ1 polymorphisms and chronic hepatitis B infection in an Iranian population. Rev Soc Bras Med Trop 2017; 50:301-308. [PMID: 28700046 DOI: 10.1590/0037-8682-0266-2016] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 03/06/2017] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION: Transforming growth factor-beta 1 (TGFβ1) is a potent suppressive cytokine that contributes to chronic hepatitis B (CHB) infection. Disparities in TGFβ1 production among individuals have been attributed to TGFβ1 genetic polymorphisms. We examined whether three putative polymorphisms in TGFβ1[-509 C/T (rs1800469), +869 C/T (rs1800470), and +11929 C/T (rs1800472)]are associated with CHB infection in a South-Eastern Iranian population. METHODS: In total, 341 subjects were recruited, including 178 patients with CHB and 163 healthy individuals as controls. Genotyping of the three TGFβ1 SNPs was performed by tetra amplification refractory mutation system-PCR. RESULTS: TheTGFβ1 +869 TT vs.CC genotype in codominant (OR=0.445, p=0.012) and TT vs. TC+CC in the recessive (OR=0.439, p=0.003) model as well as the variant allele T vs. C(OR=0.714, p=0.038) were associated with lower CHB infection risk. However, the +11929 C/T polymorphism was associated with increased CHB risk, and the CT vs. CC genotype (OR=2.77, P=0.001) and T variant allele (OR=2.53, P=0.002) were risk factors for CHB. Furthermore, TTT (+869/-509/+11929) and CCC haplotypes were risk and protective factors for CHB, respectively. We found no significant association between viral DNA load and TGFβ1 genotype or hepatic enzyme levels (p >0.05). CONCLUSIONS: Results indicated that the TGFβ1+869TT genotype and T allele were protective factors, whereas the +11929 CT genotype and T allele were risk factors for CHB infection.
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Affiliation(s)
- Ebrahim Eskandari
- Genetic of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.,Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Malihe Metanat
- Infectious Diseases & Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Elham Pahlevani
- Infectious Diseases & Tropical Medicine Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
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27
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Sanjabi S, Oh SA, Li MO. Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection. Cold Spring Harb Perspect Biol 2017; 9:cshperspect.a022236. [PMID: 28108486 DOI: 10.1101/cshperspect.a022236] [Citation(s) in RCA: 410] [Impact Index Per Article: 51.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Transforming growth factor β (TGF-β) is a pleiotropic cytokine involved in both suppressive and inflammatory immune responses. After 30 years of intense study, we have only begun to elucidate how TGF-β alters immunity under various conditions. Under steady-state conditions, TGF-β regulates thymic T-cell selection and maintains homeostasis of the naïve T-cell pool. TGF-β inhibits cytotoxic T lymphocyte (CTL), Th1-, and Th2-cell differentiation while promoting peripheral (p)Treg-, Th17-, Th9-, and Tfh-cell generation, and T-cell tissue residence in response to immune challenges. Similarly, TGF-β controls the proliferation, survival, activation, and differentiation of B cells, as well as the development and functions of innate cells, including natural killer (NK) cells, macrophages, dendritic cells, and granulocytes. Collectively, TGF-β plays a pivotal role in maintaining peripheral tolerance against self- and innocuous antigens, such as food, commensal bacteria, and fetal alloantigens, and in controlling immune responses to pathogens.
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Affiliation(s)
- Shomyseh Sanjabi
- Institute of Virology and Immunology, Gladstone Institutes, San Francisco, California 94158.,Department of Microbiology and Immunology, University of California, San Francisco, California 94143
| | - Soyoung A Oh
- Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065
| | - Ming O Li
- Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065
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28
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Trehanpati N, Vyas AK. Immune Regulation by T Regulatory Cells in Hepatitis B Virus-Related Inflammation and Cancer. Scand J Immunol 2017; 85:175-181. [PMID: 28109025 DOI: 10.1111/sji.12524] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 01/13/2017] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is the leading cause of cancer death, and hepatitis B virus (HBV) infection is one of the commonest causes in Asian countries. India has the second largest pool after China for hepatitis B-infected subjects. HBV clearance is T cell dependent, and one of the reasons for T cells hyporesponsiveness is due to mass production of regulatory T cells (Tregs) through activation of Notch signalling, which suppress CD4/CD8 T cells. Tregs are important to maintain cellular homoeostasis; however, during viral infection increase of Tregs is inversely proportional to HBV DNA titres. Tregs exert their suppressive effect either via cell-to-cell contact or through release of interleukin (IL)-2, IL-10, TGF-β and IL-35. In Chronic hepatitis B virus CHBV infection, PD-1 pathway also gets activated and is involved in promoting tolerance. However, with Tregs induction, virus-specific T cell responses also get decreased. Circulatory and intratumoural Tregs promote development of HBV-specific HCC more by decreasing and impairing the effector functions of CD8 T cells. Antiviral therapies and PD-1 blockade strategy had shown the inhibition of Tregs and reduction in HBV DNA. However, inhibition of HBV-specific Tregs is major challenge for future therapies. New cytokine blockade therapies have emerged as potential therapeutic potentials.
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Affiliation(s)
- N Trehanpati
- Departments of Molecular and cellular Medicine, Institute of Liver & Biliary Sciences, New Delhi, India
| | - A K Vyas
- Departments of Molecular and cellular Medicine, Institute of Liver & Biliary Sciences, New Delhi, India
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29
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Kariminik A, Kheirkhah B. Tumor growth factor-β is an important factor for immunosuppression and tumorgenesis in Polyoma BK virus infection; a systematic review article. Cytokine 2017; 95:64-69. [PMID: 28237875 DOI: 10.1016/j.cyto.2017.02.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2017] [Revised: 02/07/2017] [Accepted: 02/12/2017] [Indexed: 02/07/2023]
Abstract
Polyoma BK virus (PBK) is a prevalent human specific virus and the cause of several malignancies in human. The main mechanisms used by PBK to induce/stimulate human cancers are yet to be clarified but it has been proposed that PBK may use several mechanisms to induce/stimulate cancers in human including attenuation of immune responses via up-regulation of immunosuppressor molecules. Transforming growth factor beta (TGF-β) is a key multifunctional factor from modulation of immunosurveillance to angiogenesis. The key roles of TGF-β in the progression of Th17 and T regulatory subsets, the most important immune cells involved in development of cancers, have been demonstrated. Thus, this review article aims to describe the mechanisms used by PBK in induction/stimulation of human cancers in TGF-β dependent manner..
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Affiliation(s)
- Ashraf Kariminik
- Department of Microbiology, Kerman Branch, Islamic Azad University, Kerman, Iran.
| | - Babak Kheirkhah
- Department of Microbiology, Kerman Branch, Islamic Azad University, Kerman, Iran
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30
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Sepehri Z, Masoumi M, Ebrahimi N, Kiani Z, Nasiri AA, Kohan F, Sheikh Fathollahi M, Kazemi Arababadi M, Asadikaram G. Atorvastatin, Losartan and Captopril Lead to Upregulation of TGF-β, and Downregulation of IL-6 in Coronary Artery Disease and Hypertension. PLoS One 2016; 11:e0168312. [PMID: 28033321 PMCID: PMC5199082 DOI: 10.1371/journal.pone.0168312] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 11/30/2016] [Indexed: 12/29/2022] Open
Abstract
Introduction Coronary artery disease (CAD) and hypertension are the main reasons of ischemic heart diseases (IHDs). Cytokines as the small glycoproteins are the main arm of immune system and manipulate all of the cardiovascular diseases. The aim of the current study was to examine the effects of treatment of hypertension and CAD on serum levels of IL-6, IL-8, TGF-β and TNF-α. Material and Methods This interventional study was performed on the patients with hypertension without CAD (group 1), hypertension and CAD (group 2), CAD but not hypertension (group 3) and without hypertension and CAD as controls (group 4). The patients received routine treatment for hypertension and CAD. Serum levels of IL-6, IL-8, TGF-β and TNF-α were analyzed in the groups treated with various drugs, using ELISA technique. Results With regard to the medications, Atorvastatin, Losartan and Captopril were administered more in patients (groups 1, 2 and 3) than the patients without hypertension and CAD. The results revealed that serum levels of TGF-β and IL-6 were significantly increased and decreased, respectively, in the groups 1, 2 and 3 when compared to group 4. Serum levels of TGF-β were also increased in females in comparison to males in the group 4. Discussion According to the results it seems that Atorvastatin, Losartan and Captopril have reduced inflammation in in vivo conditions via downregulation of IL-6 and upregulation of TGF-β.
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Affiliation(s)
- Zahra Sepehri
- Department of Internal Medicine, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran
| | - Mohammad Masoumi
- Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
- * E-mail: ,
| | - Nazanin Ebrahimi
- Department of Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Zohre Kiani
- Student Research Committee, Zabol University of Medical Sciences, Zabol, Iran
- Department of Internal Medicine, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Ali Akbar Nasiri
- Department of Anesthesiology, Zabol University of Medical Sciences, Zabol, Iran
| | - Farhad Kohan
- Student Research Committee, Zabol University of Medical Sciences, Zabol, Iran
| | - Mahmood Sheikh Fathollahi
- Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
- Department of Social Medicine, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Mohammad Kazemi Arababadi
- Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
- Department of Laboratory Sciences, Faculty of Paramedicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Gholamreza Asadikaram
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
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Abstract
Hepatitis B virus (HBV) infection is a worldwide health problem, with approximately one third of populations have been infected, among which 3-5% of adults and more than 90% of children developed to chronic HBV infection. Host immune factors play essential roles in the outcome of HBV infection. Thus, ineffective immune response against HBV may result in persistent virus replications and liver necroinflammations, then lead to chronic HBV infection, liver cirrhosis, and even hepatocellular carcinoma. Cytokine balance was shown to be an important immune characteristic in the development and progression of hepatitis B, as well as in an effective antiviral immunity. Large numbers of cytokines are not only involved in the initiation and regulation of immune responses but also contributing directly or indirectly to the inhibition of virus replication. Besides, cytokines initiate downstream signaling pathway activities by binding to specific receptors expressed on the target cells and play important roles in the responses against viral infections and, therefore, might affect susceptibility to HBV and/or the natural course of the infection. Since cytokines are the primary causes of inflammation and mediates liver injury after HBV infection, we have discussed recent advances on the roles of various cytokines [including T helper type 1 cells (Th1), Th2, Th17, regulatory T cells (Treg)-related cytokines] in different phases of HBV infection and cytokine-related mechanisms for impaired viral control and liver damage during HBV infection. We then focus on experimental therapeutic applications of cytokines to gain a better understanding of this newly emerging aspect of disease pathogenesis.
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Zare-Bidaki M, Assar S, Hakimi H, Abdollahi SH, Nosratabadi R, Kennedy D, Arababadi MK. TGF-β in Toxoplasmosis: Friend or foe? Cytokine 2016; 86:29-35. [DOI: 10.1016/j.cyto.2016.07.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Revised: 06/29/2016] [Accepted: 07/01/2016] [Indexed: 12/17/2022]
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Wang L, Wang J, Liu Y, Wang B, Yang S, Yu Q, Roggendorf M, Lu M, Liu J, Yang D. Molecular cloning, characterization and expression analysis of TGF-β and receptor genes in the woodchuck model. Gene 2016; 595:1-8. [PMID: 27637515 DOI: 10.1016/j.gene.2016.09.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 08/22/2016] [Accepted: 09/12/2016] [Indexed: 12/16/2022]
Abstract
Transforming growth factor beta (TGF-β) is an important cytokine with pleiotropic regulatory functions in the immune system and in the responses against viral infections. TGF-β acts on a variety of immune cells through the cell surface TGF-β receptor (University of Duisburg-EssenTGFBR). The woodchuck has been used as a biomedical model for studies of obesity and energy balance, endocrine and metabolic function, cardiovascular, cerebrovascular and neoplastic disease. Woodchucks infected with woodchuck hepatitis virus (WHV) represent an informative animal model to study hepatitis B virus (HBV) infection. In this study, the cDNA sequences of woodchuck TGF-β1, TGF-β2, TGFBR1 and TGFBR2 were cloned, sequenced and characterized. The full-length TGFBR1 cDNA sequence consisted of 1305bp coding sequence (CDS) that encoded 434 amino acids with a molecular weight of 48.9kDa. The phylogenetic tree analysis revealed that the woodchuck TGF-β family genes had a closer genetic relationship with Ictidomys tridecemlineatus. One antibody with cross-reactivity to woodchuck TGFBR1 was identified by flow cytometry. Moreover, the expression of these genes were analyzed at the transcriptional level. The quantitative PCR analysis showed that the TGF-β family transcripts were constitutively expressed in many tissues tested. Altered expression levels of the TGF-β family transcripts in the liver of WHV infected woodchucks were observed. These results serve as a foundation for further insight into the role of the TGF-β family in viral hepatitis in woodchuck model. Our work also possesses the potential value for characterizing the TGF-β family in other related diseases, such as obesity-related diseases, metabolic disorder, cardiovascular disease and cancer.
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Affiliation(s)
- Lu Wang
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Junzhong Wang
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Yana Liu
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Baoju Wang
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Shangqing Yang
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Qing Yu
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China
| | - Michael Roggendorf
- Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Germany
| | - Mengji Lu
- Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Germany
| | - Jia Liu
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
| | - Dongliang Yang
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
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Bakhshi Aliabad MH, Jafari E, Karimi Kakh M, Nosratababadi R, Bakhshi H, Sheikhha MH, Bidaki R, Askari A, Kazemi Arababadi M. Anxiety leads to up-regulation of CD36 on the monocytes of chronic hepatitis B-infected patients. Int J Psychiatry Med 2016. [PMID: 28629284 DOI: 10.1177/0091217416680199] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Introduction It has been hypothesized that mental disorders including depression and anxiety can affect immune responses. The study was done to evaluate the relation between depression and anxiety and expression levels of CD36, CD68, and CD9 on peripheral blood monocytes of chronic hepatitis B (CHB) patients. Methods Sixty CHB patients were selected with various ranges of depression and anxiety. Depression and anxiety were evaluated using a standard questionnaire by an expert psychiatrist according to BECK's Depression Inventory II and Hamilton Anxiety Rating Scale, respectively. The levels of CD36, CD68, and CD9 on the peripheral blood monocytes have been performed using flow cytometry technique. Results The results demonstrated that levels of CD36 were significantly increased on the peripheral blood monocytes of CHB patients when compared with CHB patients with no anxiety. Expression levels of CD68 and CD9 were not significantly altered on the CHB patients with various ranges of anxiety. Expression levels of CD36, CD68, and CD9 were also not significantly altered on the CHB patients with various ranges of depression. Discussion It seems that anxiety induces inflammation in the CHB patients by induction of alteration in several molecules including up-regulation of CD36. CD36 plays important roles in the induction of tissue damage; hence, it may be hypothesized that anxiety may participate in the induction of some hepatitis B complications.
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Affiliation(s)
| | - Elham Jafari
- 2 Pathology and Stem Cells Research Center, Pathology Department, Afzalipour Kerman Medical Sciences University, Kerman, Iran
| | | | - Reza Nosratababadi
- 4 Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,8 Department of Immunology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Hamid Bakhshi
- 5 Department of Medical Education, Molecular and Cellular Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Mohammad Hassan Sheikhha
- 1 Department of Human Genetics, Shahid Sadoughi University of Medical Science, International Campus, Yazd, Iran
| | - Reza Bidaki
- 6 Research Center of Addiction of Behavioral Sciences, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Azade Askari
- 4 Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Mohammad Kazemi Arababadi
- 4 Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,7 Department of Laboratory Sciences, Faculty of Paramedicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
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Prevention and Therapeutic Effects and Mechanisms of Tanshinone IIA Sodium Sulfonate on Acute Liver Injury Mice Model. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 2016:4097398. [PMID: 27274751 PMCID: PMC4870345 DOI: 10.1155/2016/4097398] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Revised: 03/31/2016] [Accepted: 04/07/2016] [Indexed: 12/16/2022]
Abstract
Tanshinone IIA sodium sulfonate (TSS) is a water-soluble derivative of tanshinone IIA, which is the main pharmacologically active component of Salvia miltiorrhiza. This study aimed to verify the preventive and therapeutic effects of TSS and its combined therapeutic effects with magnesium isoglycyrrhizinate (MI) in D-galactosamine- (D-Gal-) induced acute liver injury (ALI) in mice. The potential regulatory mechanisms of TSS on ALI were also examined. Our results may provide a basis for the development of novel therapeutics for ALI.
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Tavakolpour S, Alavian SM, Sali S. Manipulation of Regulatory Cells' Responses to Treatments for Chronic Hepatitis B Virus Infection. HEPATITIS MONTHLY 2016; 16:e37927. [PMID: 27630728 PMCID: PMC5010887 DOI: 10.5812/hepatmon.37927] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 04/14/2016] [Accepted: 04/20/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Identification of effective treatments in hepatitis B virus (HBV) infection remains a controversial topic. Although the currently approved drugs for HBV control the disease's progression and also limit associated outcomes, these drugs may not fully eradicate HBV infection. In addition to better managing patients with chronic hepatitis B (CHB) infection, the induction of seroclearance by these drugs has been a commonly discussed topic in recent years. OBJECTIVES In this study, we focused on treating CHB infection via the manipulation of T cells' responses to identify possible approaches to cure CHB. MATERIALS AND METHODS All studies relevant to the role of cellular and humoral responses in HBV infection (especially regulatory cells) were investigated via a systematic search of different databases, including PubMed, Scopus, and Google Scholar. Considering extracted data and also our unpublished data regarding the association between regulatory cytokines and CHB, we introduced a novel approach for the induction of seroclearance. RESULTS Considering the increased levels of regulatory cytokines and also regulatory T cells (Tregs) during CHB, it seems that these cells are deeply involved in CHB infection. The inhibition of regulatory T cells may reverse the dysfunction of effector T cells in patients with CHB infection. In order to inhibit Tregs' responses, different types of approaches could be employed to restore the impaired function of effector T cells. The blockade of IL-10, IL-35, CTLA-4, PD-1, and TIM-3 were discussed throughout this study. Regardless of the efficacy of these methods, CHB patients may experience serious liver injuries due to the cytotoxic action of CD8+ T cells. Antiviral therapy and a decrease in HBV DNA to undetectable levels could also significantly reduce the risk of the hepatitis B flare. CONCLUSIONS The inhibition of Tregs is a novel therapeutic approach to cure chronically HBV infected patients. However, further studies are needed to investigate the safety and efficacy of this approach.
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Affiliation(s)
- Soheil Tavakolpour
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqyiatallah University of Medical Sciences, Tehran, IR Iran
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqyiatallah University of Medical Sciences, Tehran, IR Iran
- Corresponding Author: Seyed Moayed Alavian, Baqiyatallah Research Center for Gastroenterology and Liver Disease, Baqyiatallah University of Medical Sciences, Tehran, IR Iran. Tel/Fax: +98-2181264070, E-mail:
| | - Shahnaz Sali
- Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
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Kariminik A, Yaghobi R, Dabiri S. Innate Immunity and BK Virus: Prospective Strategies. Viral Immunol 2016; 29:74-82. [PMID: 26752693 DOI: 10.1089/vim.2015.0099] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Recent information demonstrated that BK virus reactivation is a dominant complication after kidney transplantation, which occurs because of immunosuppression. BK virus reactivation is the main reason of transplanted kidney losing. Immune response against BK virus is the major inhibitor of the virus reactivation. Therefore, improving our knowledge regarding the main parameters that fight against BK viruses can shed light on to direct new treatment strategies to suppress BK infection. Innate immunity consists of numerous cell systems and also soluble molecules, which not only suppress virus replication, but also activate adaptive immunity to eradicate the infection. Additionally, it appears that immune responses against reactivated BK virus are the main reasons for induction of BK virus-associated nephropathy (BKAN). Thus, improving our knowledge regarding the parameters and detailed mechanisms of innate immunity and also the status of innate immunity of the patients with BK virus reactivation and its complications can introduce new prospective strategies to either prevent or as therapy of the complication. Therefore, this review was aimed to collate the most recent data regarding the roles played by innate immunity against BK virus and also the status of innate immunity in the patients with reactivation BK virus and BKAN.
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Affiliation(s)
- Ashraf Kariminik
- 1 Shiraz Branch, Department of Microbiology, Islamic Azad University , Shiraz, Iran .,2 Fars Research and Science Branch, Department of Microbiology, Islamic Azad University , Fars, Iran
| | - Ramin Yaghobi
- 3 Shiraz Transplant Research Center, Shiraz University of Medical Sciences , Shiraz, Iran
| | - Shahriar Dabiri
- 4 Pathology and Stem Cell Research Center, Department of Pathology, Afzalipour School of Medicine, Kerman University of Medical Sciences , Kerman, Iran
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Wang Y, Wang CM, Jiang ZZ, Yu XJ, Fan CG, Xu FF, Zhang Q, Li LI, Li RF, Sun WS, Zhang ZH, Liu YG. MicroRNA-34c targets TGFB-induced factor homeobox 2, represses cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma. Oncol Lett 2015; 10:3095-3102. [PMID: 26722295 DOI: 10.3892/ol.2015.3649] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Accepted: 06/16/2015] [Indexed: 12/19/2022] Open
Abstract
MicroRNAs (miRs) are short, non-coding RNAs with post-transcriptional regulatory functions. Previous studies have demonstrated that miR-34c is involved in diverse biological processes, including carcinogenesis. The aim of the present study was to investigate the role of miR-34c and its target genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Expression levels of miR-34c and its predicted target genes were measured. The target genes were validated by a luciferase assay. The effects of miR-34c restoration were evaluated by the detection of HBV antigens, cell proliferation and apoptosis in vitro, in addition to the tumor growth in vivo. The data demonstrated that miR-34c was downregulated in HBV-associated HCC clinical tissues and HCC cell lines compared with their corresponding controls. transforming growth factor-β-induced factor homeobox 2 (TGIF2), a transcription factor repressing transforming growth factor-β (TGFβ) signaling, was observed to be upregulated and was identified as a target gene of miR-34c. The restoration of miR-34c in HepG2.2.15 cells suppressed TGIF2 expression, HBV replication and viral antigen synthesis; inhibited cell proliferation; and induced apoptosis. miR-34c also inhibited tumor growth in a mouse model. The present study indicates that miR-34c may act as a tumor suppressor by targeting TGIF2 during HBV-associated hepatocellular carcinogenesis. miR-34c and TGIF2 may represent key regulatory factors, diagnostic markers and therapeutic targets for the prevention and treatment of HBV-associated HCC.
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Affiliation(s)
- Yan Wang
- Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China
| | - Chun-Mei Wang
- Neurobiology Institute, Jining Medical University, Jining, Shandong 272067, P.R. China
| | - Zhen-Zhong Jiang
- Emergency Department, Chinese Frontier Defence Armed Police General Hospital, Shenzhen, Guangdong 510080, P.R. China
| | - Xiao-Jian Yu
- Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China
| | - Chun-Guang Fan
- Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China ; Shandong Quality Inspection Center for Medical Devices, Jinan, Shandong 250012, P.R. China
| | - Fei-Fei Xu
- Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China
| | - Qing Zhang
- Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, inan, Shandong 250012, P.R. China ; Gynecology Oncology Key Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
| | - L I Li
- Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China
| | - Rui-Feng Li
- Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China
| | - Wen-Sheng Sun
- Institute of Immunology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China
| | - Zhen-Hai Zhang
- Department of Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250012, P.R. China
| | - Yu-Gang Liu
- Department of Pathophysiology, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China
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Abdollahi SH, Ayoobi F, Khorramdelazad H, Nasiri Ahmadabadi B, Rezayati M, Kazemi Arababadi M, Zare-Bidaki M. Levels of Transforming Growth Factor-Beta After Immunization of Mice With in vivo prepared Toxoplasma gondii Excretory/Secretory Proteins. Jundishapur J Microbiol 2015; 8:e17802. [PMID: 26060564 PMCID: PMC4458350 DOI: 10.5812/jjm.8(5)2015.17802] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Revised: 04/09/2014] [Accepted: 04/15/2014] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Zoonotic parasite Toxoplasma gondii has a high prevalence in human populations. A suitable vaccine for animals can stop the transmission of infection between animal and human. OBJECTIVES The aim of this study was to evaluate in vivo prepared excretory/secretory antigens (E/SA) as a potential candidate for immunization against the parasite and its effect on the production of transforming growth factor-beta (TGF-β). MATERIALS AND METHODS Toxoplasma gondii tachyzoites were inoculated in the peritoneal cavity of mice and E/SA was harvested and used in animal immunization with and without adjuvant. Serum levels of anti-E/SA antibodies and TGF-β were measured in days 0, 3, 7, 14, 28 and 56 after immunization using ELISA technique. The measurements were statistically analyzed. RESULTS Our results showed that the serum levels of anti-E/SA immunoglobulins significantly increased in all of the immunized groups. The differences of the serum levels of TGF-β between the groups were statistically significant at days 28 and 56 after immunization with E/SA. CONCLUSIONS Based on our study, in vivo prepared E/SA may be considered as a good candidate for animal immunization.
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Affiliation(s)
- Seyed Hossein Abdollahi
- Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, IR Iran
| | - Fateme Ayoobi
- Physiology and Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, IR Iran
| | - Hossein Khorramdelazad
- Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, IR Iran
| | - Behzad Nasiri Ahmadabadi
- Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, IR Iran
| | - Mohammadtaghi Rezayati
- Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, IR Iran
| | - Mohammad Kazemi Arababadi
- Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, IR Iran
| | - Mohammad Zare-Bidaki
- Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, IR Iran
- Corresponding author: Mohammad Zare-Bidaki, Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, IR Iran. Tel: +98-3915234003, Fax: +98-3915225209, E-mail:
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Liang G, Liu G, Kitamura K, Wang Z, Chowdhury S, Monjurul AM, Wakae K, Koura M, Shimadu M, Kinoshita K, Muramatsu M. TGF-β suppression of HBV RNA through AID-dependent recruitment of an RNA exosome complex. PLoS Pathog 2015; 11:e1004780. [PMID: 25836330 PMCID: PMC4383551 DOI: 10.1371/journal.ppat.1004780] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Accepted: 03/03/2015] [Indexed: 01/15/2023] Open
Abstract
Transforming growth factor (TGF)-β inhibits hepatitis B virus (HBV) replication although the intracellular effectors involved are not determined. Here, we report that reduction of HBV transcripts by TGF-β is dependent on AID expression, which significantly decreases both HBV transcripts and viral DNA, resulting in inhibition of viral replication. Immunoprecipitation reveals that AID physically associates with viral P protein that binds to specific virus RNA sequence called epsilon. AID also binds to an RNA degradation complex (RNA exosome proteins), indicating that AID, RNA exosome, and P protein form an RNP complex. Suppression of HBV transcripts by TGF-β was abrogated by depletion of either AID or RNA exosome components, suggesting that AID and the RNA exosome involve in TGF-β mediated suppression of HBV RNA. Moreover, AID-mediated HBV reduction does not occur when P protein is disrupted or when viral transcription is inhibited. These results suggest that induced expression of AID by TGF-β causes recruitment of the RNA exosome to viral RNP complex and the RNA exosome degrades HBV RNA in a transcription-coupled manner.
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Affiliation(s)
- Guoxin Liang
- Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
- Department of Microbiology and Immunology, Columbia University, New York, New York, United States of America
| | - Guangyan Liu
- Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Kouichi Kitamura
- Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Zhe Wang
- Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
- Division of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Sajeda Chowdhury
- Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Ahasan Md Monjurul
- Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Kousho Wakae
- Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Miki Koura
- Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Miyuki Shimadu
- Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Kazuo Kinoshita
- Evolutionary Medicine, Shiga Medical Center Research Institute, Moriyama, Japan
| | - Masamichi Muramatsu
- Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
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Lin J, Wu JF, Zhang Q, Zhang HW, Cao GW. Virus-related liver cirrhosis: molecular basis and therapeutic options. World J Gastroenterol 2014; 20:6457-69. [PMID: 24914367 PMCID: PMC4047331 DOI: 10.3748/wjg.v20.i21.6457] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 01/10/2014] [Accepted: 03/08/2014] [Indexed: 02/07/2023] Open
Abstract
Chronic infections with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the major causes of cirrhosis globally. It takes 10-20 years to progress from viral hepatitis to cirrhosis. Intermediately active hepatic inflammation caused by the infections contributes to the inflammation-necrosis-regeneration process, ultimately cirrhosis. CD8(+) T cells and NK cells cause liver damage via targeting the infected hepatocytes directly and releasing pro-inflammatory cytokine/chemokines. Hepatic stellate cells play an active role in fibrogenesis via secreting fibrosis-related factors. Under the inflammatory microenvironment, the viruses experience mutation-selection-adaptation to evade immune clearance. However, immune selection of some HBV mutations in the evolution towards cirrhosis seems different from that towards hepatocellular carcinoma. As viral replication is an important driving force of cirrhosis pathogenesis, antiviral treatment with nucleos(t)ide analogs is generally effective in halting the progression of cirrhosis, improving liver function and reducing the morbidity of decompensated cirrhosis caused by chronic HBV infection. Interferon-α plus ribavirin and/or the direct acting antivirals such as Vaniprevir are effective for compensated cirrhosis caused by chronic HCV infection. The standard of care for the treatment of HCV-related cirrhosis with interferon-α plus ribavirin should consider the genotypes of IL-28B. Understanding the mechanism of fibrogenesis and hepatocyte regeneration will facilitate the development of novel therapies for decompensated cirrhosis.
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Ebrahim M, Bagheri V, Arababadi MK. Potential roles played by IL-6 in hepatitis B infection. Future Virol 2014. [DOI: 10.2217/fvl.14.21] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
ABSTRACT: Hepatitis B is a main disorder of the liver, which is induced by HBV. Hepatitis B can induce liver diseases, such as inflammation, cirrhosis and hepatocellular carcinoma (HCC). Recent studies demonstrated that several patients are unable to eradicate the virus from hepatocytes and develop chronic hepatitis B infections. The main mechanisms responsible for development of chronic hepatitis B and its related cirrhosis as well as HCC are yet to be identified. IL-6 is a proinflammatory cytokine that participates in stimulation of immune responses against viral infections. In addition, it has been documented that IL-6 can play key roles in induction of fibrosis and cancers. Therefore, the aim of this article is to clarify the main roles of IL-6 in stimulation of appropriate immune responses against hepatitis B virus and induction of hepatitis B-dependent cirrhosis as well as HCC.
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Affiliation(s)
- Maryam Ebrahim
- Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Vahid Bagheri
- Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Mohammad Kazemi Arababadi
- Immunology of Infectious Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
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IL-17A in hepatitis B infection: friend or foe? Arch Virol 2014; 159:1883-8. [PMID: 24532300 DOI: 10.1007/s00705-014-2002-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2013] [Accepted: 01/21/2014] [Indexed: 12/24/2022]
Abstract
Hepatitis B virus (HBV) is one of the most prevalent and infectious agents that leads to liver disease in humans. Five clinical forms of HBV infection exist, including fulminant, acute, chronic, asymptomatic and occult. The chronic, asymptomatic and occult forms are long-term infections that can lead to hepatocellular carcinoma (HCC) and liver cirrhosis. The mechanisms responsible for progression of these forms of the infection to HCC and liver cirrhosis are not yet clearly understood or characterised. However, genetic and immunological parameters may play important roles in the disease. IL-17A is an important cytokine involved in early immune responses against fungal and bacterial infections, but its role in the response against viral infections is yet to be fully clarified. The crucial roles of IL-17A in the pathogenesis of autoimmune and destructive immune-related diseases have been documented and may provide insights into its functions during hepatitis infection. Therefore, the aim of this review was to address the recent information regarding the status and association of IL-17A during hepatitis B infection and its related disorders, including HCC and liver cirrhosis.
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