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Schwertheim S, Alhardan M, Manka PP, Sowa JP, Canbay A, Schmidt HHJ, Baba HA, Kälsch J. Higher pNRF2, SOCS3, IRF3, and RIG1 Tissue Protein Expression in NASH Patients versus NAFL Patients: pNRF2 Expression Is Concomitantly Associated with Elevated Fasting Glucose Levels. J Pers Med 2023; 13:1152. [PMID: 37511764 PMCID: PMC10381647 DOI: 10.3390/jpm13071152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 07/05/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) embraces simple steatosis in non-alcoholic fatty liver (NAFL) to advanced non-alcoholic steatohepatitis (NASH) associated with inflammation, fibrosis, and cirrhosis. NAFLD patients often have metabolic syndrome and high risks of cardiovascular and liver-related mortality. Our aim was to clarify which proteins play a role in the progression of NAFL to NASH. The study investigates paraffin-embedded samples of 22 NAFL and 33 NASH patients. To detect potential candidates, samples were analyzed by immunohistochemistry for the proteins involved in innate immune regulation, autophagy, apoptosis, and antioxidant defense: IRF3, RIG-1, SOCS3, pSTAT3, STX17, SGLT2, Ki67, M30, Caspase 3, and pNRF2. The expression of pNRF2 immunopositive nuclei and SOCS3 cytoplasmic staining were higher in NASH than in NAFL (p = 0.001); pNRF2 was associated with elevated fasting glucose levels. SOCS3 immunopositivity correlated positively with RIG1 (r = 0.765; p = 0.001). Further, in NASH bile ducts showed stronger IRF3 immunostaining than in NAFL (p = 0.002); immunopositive RIG1 tissue was higher in NASH than in NAFL (p = 0.01). Our results indicate that pNRF2, SOCS3, IRF3, and RIG1 are involved in hepatic lipid metabolism. We suggest that they may be suitable for further studies to assess their potential as therapeutics.
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Affiliation(s)
- Suzan Schwertheim
- Department of Gastroenterology, Hepatology and Transplant Medicine, University Hospital of Essen, University of Duisburg-Essen, 45147 Essen, Germany
- Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Malek Alhardan
- Department of Gastroenterology, Hepatology and Transplant Medicine, University Hospital of Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Paul P Manka
- Department of Medicine, Ruhr University Bochum, University Hospital Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany
| | - Jan-Peter Sowa
- Department of Medicine, Ruhr University Bochum, University Hospital Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany
| | - Ali Canbay
- Department of Medicine, Ruhr University Bochum, University Hospital Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany
| | - Hartmut H-J Schmidt
- Department of Gastroenterology, Hepatology and Transplant Medicine, University Hospital of Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Hideo A Baba
- Institute of Pathology, University Hospital of Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Julia Kälsch
- Department of Gastroenterology, Hepatology and Transplant Medicine, University Hospital of Essen, University of Duisburg-Essen, 45147 Essen, Germany
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Quelhas P, Cerski C, Dos Santos JL. Update on Etiology and Pathogenesis of Biliary Atresia. Curr Pediatr Rev 2022; 19:48-67. [PMID: 35538816 DOI: 10.2174/1573396318666220510130259] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/16/2022] [Accepted: 02/15/2022] [Indexed: 01/31/2023]
Abstract
Biliary atresia is a rare inflammatory sclerosing obstructive cholangiopathy that initiates in infancy as complete choledochal blockage and progresses to the involvement of intrahepatic biliary epithelium. Growing evidence shows that biliary atresia is not a single entity with a single etiology but a phenotype resulting from multifactorial events whose common path is obliterative cholangiopathy. The etiology of biliary atresia has been explained as resulting from genetic variants, toxins, viral infection, chronic inflammation or bile duct lesions mediated by autoimmunity, abnormalities in the development of the bile ducts, and defects in embryogenesis, abnormal fetal or prenatal circulation and susceptibility factors. It is increasingly evident that the genetic and epigenetic predisposition combined with the environmental factors to which the mother is exposed are potential triggers for biliary atresia. There is also an indication that a progressive thickening of the arterial middle layer occurs in this disease, suggestive of vascular remodeling and disappearance of the interlobular bile ducts. It is suggested that the hypoxia/ischemia process can affect portal structures in biliary atresia and is associated with both the extent of biliary proliferation and the thickening of the medial layer.
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Affiliation(s)
- Patrícia Quelhas
- CICS-UBI - Centro de Investigação em Ciências da Saúde, University of Beira Interior, 6200-506 Covilhã, Portugal
| | - Carlos Cerski
- Department of Pathology, University Federal Rio Grande do Sul, 90040-060, Porto Alegre, Brasil
| | - Jorge Luiz Dos Santos
- CICS-UBI - Centro de Investigação em Ciências da Saúde, University of Beira Interior, 6200-506 Covilhã, Portugal
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He K, Feng Y, An S, Liu F, Xiang G. Integrative epigenomic profiling reveal AP-1 is a key regulator in intrahepatich cholangiocarcinoma. Genomics 2021; 114:241-252. [PMID: 34942351 DOI: 10.1016/j.ygeno.2021.12.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 04/19/2021] [Accepted: 12/14/2021] [Indexed: 01/14/2023]
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor with poor prognosis while its mechanisms of pathogenesis remain elusive. In this study, we performed systemic epigenomic and transcriptomic profiling via MNase-seq, ChIP-seq and RNA-seq in normal cholangiocyte and ICC cell lines. We showed that active histone modifications (H3K4me3, H3K4me1 and H3K27ac) were less enriched on cancer-related genes in ICC cell lines compared to control. The region of different histone modification patterns is enrichment in sites of AP-1 motif. Subsequent analysis showed that ICC had different nucleosome occupancy in differentially expressed genes compared to a normal cell line. Furthermore, we found that AP-1 plays a key role in ICC and regulates ICC-related genes through its AP-1 binding site. This study is the first report showing the global features of histone modification, transcript, and nucleosome profiles in ICC; we also show that the transcription factor AP-1 might be a key target gene in ICC.
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Affiliation(s)
- Ke He
- Department of General Surgery, Guangdong Second Provincial General Hospital, Guangzhou 510317, China; Department of Biochemistry, Zhongshan School of Medicine; Center for Stem Cell Biology and Tissue Engineering, Key laboratory of ministry of education, Sun Yat-sen University, Guangzhou 510080, China
| | - Yuliang Feng
- Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, OX37LD, United Kingdom
| | - Sanqi An
- Department of General Surgery, Guangdong Second Provincial General Hospital, Guangzhou 510317, China; Department of Biochemistry, Zhongshan School of Medicine; Center for Stem Cell Biology and Tissue Engineering, Key laboratory of ministry of education, Sun Yat-sen University, Guangzhou 510080, China
| | - Fei Liu
- Department of General Surgery, Guangdong Second Provincial General Hospital, Guangzhou 510317, China
| | - Guoan Xiang
- Department of General Surgery, Guangdong Second Provincial General Hospital, Guangzhou 510317, China.
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Zhang Q, Duan HX, Li RL, Sun JY, Liu J, Peng W, Wu CJ, Gao YX. Inducing Apoptosis and Suppressing Inflammatory Reactions in Synovial Fibroblasts are Two Important Ways for Guizhi-Shaoyao-Zhimu Decoction Against Rheumatoid Arthritis. J Inflamm Res 2021; 14:217-236. [PMID: 33542641 PMCID: PMC7851583 DOI: 10.2147/jir.s287242] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 12/02/2020] [Indexed: 12/27/2022] Open
Abstract
Background and Objectives Guizhi-Shaoyao-Zhimu decoction (GSZD) is often applied to control rheumatoid arthritis (RA), gout, osteoarthritis, etc. In this study, bioinformatic analysis and experimental verification were used to uncover the integral mechanism profile of GSZD against RA. Materials and Methods The chemical compositions of GSZD were identified by UPLC-QTOF-MS/MS. MH7A cell model was established to screen active compounds in GSZD, and potential targets of these compounds were predicted through online database retrieval. The differential expression genes (DEGs) in synovial tissue of RA patients and normal controls were retrieved from the GEO database. DEGs and the predicated compounds targets were overlapped, and the overlapped genes were subsequently enriched by GO and KEGG analysis. The pathways with significant enrichments were further experimentally verified. Results A total of 19 constituents were identified from GSZD, and 11 compounds showed obviously antiproliferative effects on MH7A cells with IC50 < 100 μg/mL. Bioinformatic analysis indicated that IL-1β, IL-6, MAPK8, JAK2, CXCL8, and CASP3 were the main targets of GSZD, and the integral pharmacological mechanisms profile of GSZD might be related to anti-inflammation and proapoptosis. GSZD can promote the loss of mitochondrial membrane potential (MOMP) and induce apoptosis in MH7A cells. Furthermore, in vitro experiments showed GSZD can not only downregulate mRNA expressions of IL-1β (p<0.05), IL-6 (p<0.05), MMPs (p<0.05) and CCL5 (p<0.05) but also inhibit the nuclear transcription of NF-κB. GSZD also reduced the expressions of Bcl-2 (p<0.05), JAK2 (p<0.05), STAT-3 (p<0.05), whereas increase Bax (p<0.05), Caspase-3 (p<0.05) and caspase-9 (p<0.05). Conclusion Collectively, inducing synovial fibroblast apoptosis and inhibiting inflammatory response are two important ways for GSZD to RA, and our study proved bioinformatic analysis combined with experimental verification is a feasible method to explore the drug targets and mechanism of actions of TCMs.
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Affiliation(s)
- Qing Zhang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, People's Republic of China
| | - Hu-Xinyue Duan
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, People's Republic of China
| | - Ruo-Lan Li
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, People's Republic of China
| | - Jia-Yi Sun
- Innovation Research Institute, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, People's Republic of China
| | - Jia Liu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, People's Republic of China
| | - Wei Peng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, People's Republic of China
| | - Chun-Jie Wu
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611130, People's Republic of China
| | - Yong-Xiang Gao
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, People's Republic of China
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Shiratori T, Imaizumi T, Hirono K, Kawaguchi S, Matsumiya T, Seya K, Tasaka S. ISG56 is involved in CXCL10 expression induced by TLR3 signaling in BEAS-2B bronchial epithelial cells. Exp Lung Res 2020; 46:195-202. [PMID: 32363951 DOI: 10.1080/01902148.2020.1760965] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Purpose and aim of the study: Bronchial epithelial cells play an important role in immune response against viral infections. Toll-like receptor 3 (TLR3) is a pathogen recognition receptor that recognizes viral double-stranded RNA (dsRNA). Activation of TLR3 induces the expression of interferon (IFN)-β, and newly synthesized IFN-β exhibits anti-viral activity by upregulating the expression of IFN-stimulated genes (ISGs). ISG56 encodes a multifunctional protein with tetratricopeptide motifs and is involved in anti-viral reactions through various mechanisms. Expression of chemokines such as CXCL10, which induces leukocyte chemotaxis, is essential for defense against airway microbes. However, regulation of chemokine expression by ISG56 in bronchial epithelial cells has not been fully investigated. The aim of this study was to examine the expression of ISG56 and its role in CXCL10 production in BEAS-2B bronchial epithelial cells treated with dsRNA.Materials and methods: BEAS-2B bronchial epithelial cells were treated with polyinosinic-polycytidylic acid (poly IC), a synthetic TLR3 ligand. The mRNA and protein expression levels of ISG 56 were analyzed by quantitative reverse transcription polymerase chain reaction and western blotting. The effect of knocking down TLR3, IFN-β, and ISG56 was examined using RNA interference. The protein expression of CXCL10 in culture medium was measured using an enzyme-linked immunosorbent assay.Results: Poly IC induced ISG56 expression in a concentration- and time- dependent manner. RNA interference showed that ISG56 induction was inhibited by knockdown of TLR3 or IFN-β and that ISG 56 knockdown decreased CXCL10 expression.Conclusions: ISG56 was induced by poly IC through TLR3/IFN-β axis, and ISG56 may positively regulated CXCL10 expression in BEAS-2B cells. ISG56 may modulate anti-viral innate immunity, at least in part, by regulating the expression of CXCL10 in bronchial epithelial cells.
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Affiliation(s)
- Toshihiro Shiratori
- Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Tadaatsu Imaizumi
- Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Koji Hirono
- Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Shogo Kawaguchi
- Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Tomoh Matsumiya
- Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Kazuhiko Seya
- Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Sadatomo Tasaka
- Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
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Tang YM, Yu HY. Progress in research of mechanism of biliary epithelial cell injury in primary biliary cholangitis. Shijie Huaren Xiaohua Zazhi 2019; 27:36-42. [DOI: 10.11569/wcjd.v27.i1.36] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by chronic biliary cholestasis and progressive intrahepatic and small bile duct non- suppurative inflammation with early infiltration of inflammatory cells around biliary epithelial cells (BECs). BECs lining the bile duct express multiple receptors for pathogen-associated molecular patterns and can activate intracellular signaling pathways and participate in immune regulation. The etiology and pathogenesis of PBC are not fully understood yet, but the key step found in its pathogenesis is the targeted destruction of biliary cells. Since bile duct epithelial cells participate in a series of intrahepatic immune regulation processes, bile duct epithelial cell injury is an important mechanism involved in the development of intrahepatic inflammation in PBC. Therefore, understanding the mechanism of BEC injury can help us find some new targets for the treatment of PBC. This article briefly reviews the progress in the research of mechanism of biliary epithelial cell injury in PBC.
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Affiliation(s)
- Ying-Mei Tang
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
| | - Hai-Yan Yu
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
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Wu Y, Liu T, Yuan Y, Zhang Z. Gene expression profile of TLR7 signaling pathway in the liver of rhesus rotavirus-induced murine biliary atresia. Biochem Biophys Res Commun 2018; 503:291-296. [PMID: 29909011 DOI: 10.1016/j.bbrc.2018.06.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Accepted: 06/07/2018] [Indexed: 01/06/2023]
Abstract
PURPOSE To identify genes potentially involved in the pathogenesis of bile duct obstruction in biliary atresia (BA). METHODS We used rhesus rotavirus (RRV) Balb/c mouse BA model to study BA. Liver and serum samples were harvested from BA and normal control (NC) groups at 1, 3, 5, 7, 10 and 14 days postinoculation. Serum total bilirubin (STB) and conjugated bilirubin (CB) were measured. Livers of each group at day 7 were used for a genome-wide expression analysis. Expression of TLR7 signaling pathway in liver was measured by immunohistochemical staining and western blotting, including expression of TLR7, activation of phosphorylated IRF7 and secretion of IFN-β, IL-1α and IL-6. Cell viability and survival rate after RRV infection were measured by using TLR7 knockdown human cholangiocarcinoma cell RBE. RESULTS STB was significantly elevated from day 5 postinoculation and CB was from day 7 postinoculation, while CK19 (the biomarker of biliary epithelial cells) expression by western blotting was decreased. By microarray analysis of liver tissues at day 7 postinoculation, TLR7 signaling pathway was up-regulated in BA mice. Based on the results of microarray analysis, the protein expression of TLR7 in the liver tissues of BA groups were found to be up-regulated from day 5 comparing to respective NC groups, although it was increased as pups aged in NC groups. And the level of p-IRF7 and secretion of cytokines were also statistically significant in BA groups. In vitro, TLR7 knockdown cell line showed less cellular proliferation and more susceptible to RRV infection. CONCLUSION By in vivo study, TLR7 signal pathway was up-regulated in BA group; by additional in vitro study, intact TLR7 signal pathway might have some protective abilities in BA pathogenesis.
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Affiliation(s)
- Yue Wu
- Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, 110004, PR China
| | - Tingzheng Liu
- Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, 110004, PR China
| | - Yuhang Yuan
- Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, PR China
| | - Zhibo Zhang
- Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, 110004, PR China.
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Yang XB, Jiang H, Shi Y. WITHDRAWN: SIKE1 deficiency accelerates hepatic ischemia/reperfusion (IR) injury through enhancing Toll-like receptor-3-regulated inflammation. Biochem Biophys Res Commun 2018:S0006-291X(18)30140-2. [PMID: 29366783 DOI: 10.1016/j.bbrc.2018.01.125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 01/19/2018] [Indexed: 06/07/2023]
Abstract
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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Affiliation(s)
- Xiao-Bo Yang
- Department of Neonatology, The Central Hospital of Wuhan, Wuhan 430014, China
| | - Hong Jiang
- Department of Neonatology, The Central Hospital of Wuhan, Wuhan 430014, China
| | - Yao Shi
- Department of Neonatology, The Central Hospital of Wuhan, Wuhan 430014, China
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Pang SY, Dai YM, Zhang RZ, Chen YH, Peng XF, Fu J, Chen ZR, Liu YF, Yang LY, Wen Z, Yu JK, Liu HY. Autoimmune liver disease-related autoantibodies in patients with biliary atresia. World J Gastroenterol 2018; 24:387-396. [PMID: 29391761 PMCID: PMC5776400 DOI: 10.3748/wjg.v24.i3.387] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 12/14/2017] [Accepted: 12/20/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the prevalence and clinical significance of autoimmune liver disease (ALD)-related autoantibodies in patients with biliary atresia (BA).
METHODS Sera of 124 BA patients and 140 age-matched non-BA controls were assayed for detection of the following autoantibodies: ALD profile and specific anti-nuclear antibodies (ANAs), by line-blot assay; ANA and anti-neutrophil cytoplasmic antibody (ANCA), by indirect immunofluorescence assay; specific ANCAs and anti-M2-3E, by enzyme linked immunosorbent assay. Associations of these autoantibodies with the clinical features of BA (i.e., cytomegalovirus infection, degree of liver fibrosis, and short-term prognosis of Kasai procedure) were evaluated by Spearman’s correlation coefficient.
RESULTS The overall positive rate of serum autoantibodies in preoperative BA patients was 56.5%. ALD profile assay showed that the positive reaction to primary biliary cholangitis-related autoantibodies in BA patients was higher than that to autoimmune hepatitis-related autoantibodies. Among these autoantibodies, anti-BPO was detected more frequently in the BA patients than in the controls (14.8% vs 2.2%, P < 0.05). Accordingly, 32 (25.8%) of the 124 BA patients also showed a high positive reaction for anti-M2-3E. By comparison, the controls had a remarkably lower frequency of anti-M2-3E (P < 0.05), with 6/92 (8.6%) of patients with other liver diseases and 2/48 (4.2%) of healthy controls. The prevalence of ANA in BA patients was 11.3%, which was higher than that in disease controls (3.3%, P < 0.05), but the reactivity to specific ANAs was only 8.2%. The prevalence of ANCAs (ANCA or specific ANCAs) in BA patients was also remarkably higher than that in the healthy controls (37.9% vs 6.3%, P < 0.05), but showed no difference from that in patients with other cholestasis. ANCA positivity was closely associated with the occurrence of postoperative cholangitis (r = 0.61, P < 0.05), whereas none of the autoantibodies showed a correlation to cytomegalovirus infection or the stages of liver fibrosis.
CONCLUSION High prevalence of autoantibodies in the BA developmental process strongly reveals the autoimmune-mediated pathogenesis. Serological ANCA positivity may be a useful predictive biomarker of postoperative cholangitis.
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MESH Headings
- Antibodies, Antineutrophil Cytoplasmic/blood
- Antibodies, Antineutrophil Cytoplasmic/immunology
- Antibodies, Antinuclear/blood
- Autoantigens/immunology
- Biliary Atresia/blood
- Biliary Atresia/immunology
- Biliary Atresia/surgery
- Biomarkers/blood
- Cholangitis, Sclerosing/blood
- Cholangitis, Sclerosing/immunology
- Cytomegalovirus/isolation & purification
- Cytomegalovirus Infections/blood
- Cytomegalovirus Infections/immunology
- Cytomegalovirus Infections/virology
- Enzyme-Linked Immunosorbent Assay
- Female
- Fluorescent Antibody Technique, Indirect
- Hepatitis, Autoimmune/blood
- Hepatitis, Autoimmune/immunology
- Humans
- Infant
- Liver Cirrhosis/blood
- Liver Cirrhosis/immunology
- Male
- Portoenterostomy, Hepatic/adverse effects
- Portoenterostomy, Hepatic/methods
- Postoperative Complications/blood
- Postoperative Complications/epidemiology
- Postoperative Complications/etiology
- Preoperative Period
- Prognosis
- Retrospective Studies
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Affiliation(s)
- Shu-Yin Pang
- Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
| | - Yu-Mei Dai
- Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
| | - Rui-Zhong Zhang
- Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
| | - Yi-Hao Chen
- Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
| | - Xiao-Fang Peng
- Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
| | - Jie Fu
- Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
| | - Zheng-Rong Chen
- Department of Pathology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
| | - Yun-Feng Liu
- Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
| | - Li-Yuan Yang
- Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
| | - Zhe Wen
- Department of Neonatal Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
| | - Jia-Kang Yu
- Department of Neonatal Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
| | - Hai-Ying Liu
- Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
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Yoshida H, Imaizumi T, Matsumiya T, Seya K, Kawaguchi S, Tanaka H. Gnetin C suppresses double-stranded RNA-induced C-C motif chemokine ligand 2 (CCL2) and CCL5 production by inhibiting Toll-like receptor 3 signaling pathway. Biomed Res 2018; 39:231-240. [PMID: 30333430 DOI: 10.2220/biomedres.39.231] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The innate immune system is a prerequisite for biophylactic ability, but its dysregulation can cause inflammatory and autoimmune diseases. To determine a safe method of controlling inflammatory reactions in the brain, we examined the effects of gnetin C, a natural resveratrol dimer, on C-C motif chemokine ligand 2 (CCL2) and CCL5 (pro-inflammatory chemokines) production observed after treatment with polyinosinic-polycytidylic acid [poly IC; a synthetic analog of dsRNA as a Toll-like receptor 3 (TRL3) ligand, 30 μg/mL] in cultured human astrocytoma U373MG and neuroblastoma SH-SY5Y cells. The addition of gnetin C (10 μM) to the media moderately reduced the CCL2 production and markedly suppressed CCL5 production in both cells. In the TLR3-interferon (IFN)-β-phosphorylated-STAT1 (signal transducer and activator of transcription protein 1)RIG-I (retinoic acid-inducible gene-I) pathway that mediates CCL2 and CCL5 production, gnetin C first inhibits IFN-β expression in SH-SY5Y cells and primarily inhibits STAT1 phosphorylation in U373MG cells. In any case, gnetin C attenuated the dsRNA-activated TLR3 signaling resulting in CCL2 and CCL5 production, thus, may be useful for controlling TLR3-mediated inflammation in the brain.
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Affiliation(s)
- Hidemi Yoshida
- Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine
| | - Tadaatsu Imaizumi
- Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine
| | - Tomoh Matsumiya
- Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine
| | - Kazuhiko Seya
- Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine
| | - Shogo Kawaguchi
- Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine
| | - Hiroshi Tanaka
- Department of Pediatrics, Hirosaki University Graduate School of Medicine
- Department of School Health Science, Faculty of Education
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