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Li Y, Gong L, Weng L, Pan X, Liu C, Li M. Interleukin-39 exacerbates concanavalin A-induced liver injury. Immunopharmacol Immunotoxicol 2021; 43:94-99. [PMID: 33412981 DOI: 10.1080/08923973.2020.1869778] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
BACKGROUND Interleukin (IL)-39 is a novel member of IL-12 family and has been reported to play a pro-inflammatory role in lupus-like mice, but its function in concanavalin A (ConA)-induced liver injury is currently unclear. MATERIALS AND METHODS In this study, we investigated the effects of IL-39 expression in a mouse model of ConA induced-hepatitis. We first showed that delivery of plasmid DNA encoding mouse IL-39 using the hydrodynamic tail vein injection method increased IL-39 mRNA and protein levels in the liver. We then administrated mice with IL-39 plasmid before ConA injection and measured serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, inflammatory infiltration, and hepatocyte necrosis in the liver. Additionally, we further explored the potential mechanism of IL-39 in ConA-induced liver injury by measuring several inflammatory mediators. RESULTS We found that ectopic IL-39 expression promoted the ConA-induced increase in serum ALT and AST levels, inflammatory infiltration, and hepatocyte necrosis in the liver. We also observed that IL-39 plasmid administration significantly increased serum and liver interferon-γ, tumor necrosis factor-α, and IL-17A levels, but did not affect serum and liver IL-10 levels in ConA-induced hepatitis. CONCLUSION Our results suggest that IL-39 can exacerbate ConA-induced hepatitis and may be a therapeutic target in inflammatory liver disease.
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Affiliation(s)
- Yan Li
- The Affiliated Hospital of Medical School of Ningbo University, and Department of Immunology, Ningbo University School of Medicine, Ningbo, China
| | - Luping Gong
- The Affiliated Hospital of Medical School of Ningbo University, and Department of Immunology, Ningbo University School of Medicine, Ningbo, China.,School of Marine Sciences, Ningbo University, Ningbo, China
| | - Linjie Weng
- The Affiliated Hospital of Medical School of Ningbo University, and Department of Immunology, Ningbo University School of Medicine, Ningbo, China.,School of Marine Sciences, Ningbo University, Ningbo, China
| | - Xiuhe Pan
- The Affiliated Hospital of Medical School of Ningbo University, and Department of Immunology, Ningbo University School of Medicine, Ningbo, China
| | - Chaobo Liu
- The Affiliated Hospital of Medical School of Ningbo University, and Department of Immunology, Ningbo University School of Medicine, Ningbo, China
| | - Mingcai Li
- The Affiliated Hospital of Medical School of Ningbo University, and Department of Immunology, Ningbo University School of Medicine, Ningbo, China
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Peng X, Pan X, Tan J, Li Y, Li M. Protective effect of interleukin-36 receptor antagonist on liver injury induced by concanavalin A in mice. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2020; 23:623-628. [PMID: 32742600 PMCID: PMC7374990 DOI: 10.22038/ijbms.2020.35614.8492] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective(s): Interleukin-36 receptor antagonist (IL-36Ra) is a new member of the IL-1 family that exhibits anti-inflammatory activity in a variety of inflammatory and immune diseases. Our purpose was to determine the effect of IL-36Ra on liver injury in a mouse hepatitis model induced by concanavalin A (ConA). Materials and Methods: Mice were treated with IL-36Ra DNA or pcDNA3.1 control plasmid using a hydrodynamic gene delivery approach. Results: Our data reveal that treatment with IL-36Ra decreased liver inflammation and serum level of aminotransferases. Furthermore, IL-36Ra reduced ConA-induced pro-inflammatory cytokines (interferon-γ, tumor necrosis factor-α, and IL-17A) production when compared to control plasmid. Conclusion: Our results demonstrated that IL-36Ra is a critical protector against ConA-induced liver injury.
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Affiliation(s)
- Xiao Peng
- Department of Immunology, Medical School of Ningbo University, Ningbo 315211, China
| | - Xiuhe Pan
- Department of Immunology, Medical School of Ningbo University, Ningbo 315211, China
| | - Jun Tan
- Department of Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China
| | - Yan Li
- Department of Immunology, Medical School of Ningbo University, Ningbo 315211, China
| | - Mingcai Li
- Department of Immunology, Medical School of Ningbo University, Ningbo 315211, China
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The B7x Immune Checkpoint Pathway: From Discovery to Clinical Trial. Trends Pharmacol Sci 2019; 40:883-896. [PMID: 31677920 DOI: 10.1016/j.tips.2019.09.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2019] [Revised: 09/12/2019] [Accepted: 09/13/2019] [Indexed: 12/20/2022]
Abstract
B7x (B7 homolog x, also known as B7-H4, B7S1, and VTCN1) was discovered by ourselves and others in 2003 as the seventh member of the B7 family. It is an inhibitory immune checkpoint of great significance to human disease. Tissue-expressed B7x minimizes autoimmune and inflammatory responses. It is overexpressed in a broad spectrum of human cancers, where it suppresses antitumor immunity. Further, B7x and PD-L1 tend to have mutually exclusive expression in cancer cells. Therapeutics targeting B7x are effective in animal models of cancers and autoimmune disorders, and early-phase clinical trials are underway to determine the efficacy and safety of targeting B7x in human diseases. It took 15 years moving from the discovery of B7x to clinical trials. Further studies will be necessary to identify its receptors, reveal its physiological functions in organs, and combine therapies targeting B7x with other treatments.
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Saha A, Taylor PA, Lees CJ, Panoskaltsis-Mortari A, Osborn MJ, Feser CJ, Thangavelu G, Melchinger W, Refaeli Y, Hill GR, Munn DH, Murphy WJ, Serody JS, Maillard I, Kreymborg K, van den Brink M, Dong C, Huang S, Zang X, Allison JP, Zeiser R, Blazar BR. Donor and host B7-H4 expression negatively regulates acute graft-versus-host disease lethality. JCI Insight 2019; 4:127716. [PMID: 31578305 DOI: 10.1172/jci.insight.127716] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 08/23/2019] [Indexed: 12/30/2022] Open
Abstract
B7-H4 is a negative regulatory B7 family member. We investigated the role of host and donor B7-H4 in regulating acute graft-versus-host disease (GVHD). Allogeneic donor T cells infused into B7-H4-/- versus WT recipients markedly accelerated GVHD-induced lethality. Chimera studies pointed toward B7-H4 expression on host hematopoietic cells as more critical than parenchymal cells in controlling GVHD. Rapid mortality in B7-H4-/- recipients was associated with increased donor T cell expansion, gut T cell homing and loss of intestinal epithelial integrity, increased T effector function (proliferation, proinflammatory cytokines, cytolytic molecules), and reduced apoptosis. Higher metabolic demands of rapidly proliferating donor T cells in B7-H4-/- versus WT recipients required multiple metabolic pathways, increased extracellular acidification rates (ECARs) and oxygen consumption rates (OCRs), and increased expression of fuel substrate transporters. During GVHD, B7-H4 expression was upregulated on allogeneic WT donor T cells. B7-H4-/- donor T cells given to WT recipients increased GVHD mortality and had function and biological properties similar to WT T cells from allogeneic B7-H4-/- recipients. Graft-versus-leukemia responses were intact regardless as to whether B7-H4-/- mice were used as hosts or donors. Taken together, these data provide new insights into the negative regulatory processes that control GVHD and provide support for developing therapeutic strategies directed toward the B7-H4 pathway.
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Affiliation(s)
- Asim Saha
- Masonic Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA
| | - Patricia A Taylor
- Masonic Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA
| | - Christopher J Lees
- Masonic Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA
| | - Angela Panoskaltsis-Mortari
- Masonic Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA
| | - Mark J Osborn
- Masonic Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA
| | - Colby J Feser
- Masonic Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA
| | - Govindarajan Thangavelu
- Masonic Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA
| | - Wolfgang Melchinger
- Department of Hematology, Oncology, and Stem-Cell Transplantation, Freiburg University Medical Center, Albert Ludwigs University Freiburg, Freiburg, Germany
| | - Yosef Refaeli
- Department of Dermatology, University of Colorado, Aurora, Colorado, USA
| | - Geoffrey R Hill
- Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, USA
| | - David H Munn
- Department of Pediatrics, Georgia Health Sciences University, Augusta, Georgia, USA
| | - William J Murphy
- Department of Dermatology, UC Davis School of Medicine, Sacramento, California, USA
| | - Jonathan S Serody
- Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Ivan Maillard
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Katharina Kreymborg
- Department of Immunology and Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Marcel van den Brink
- Department of Immunology and Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Chen Dong
- Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Shuyu Huang
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA
| | - Xingxing Zang
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA
| | - James P Allison
- Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Robert Zeiser
- Department of Hematology, Oncology, and Stem-Cell Transplantation, Freiburg University Medical Center, Albert Ludwigs University Freiburg, Freiburg, Germany
| | - Bruce R Blazar
- Masonic Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA
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Tang HH, Li HL, Li YX, You Y, Guan YY, Zhang SL, Liu LX, Bao WL, Zhou Y, Shen XY. Protective effects of a traditional Chinese herbal formula Jiang-Xian HuGan on Concanavalin A-induced mouse hepatitis via NF-κB and Nrf2 signaling pathways. JOURNAL OF ETHNOPHARMACOLOGY 2018; 217:118-125. [PMID: 29421593 DOI: 10.1016/j.jep.2018.02.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Revised: 01/31/2018] [Accepted: 02/03/2018] [Indexed: 05/21/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Jiang-Xian HuGan (JXHG) formulated by five natural products including Freshwater clam (Corbicula fluminea), Curcuma longa L., Ligustrum lucidum, Eclipta prostrata (L.) L. and Paeonia lactiflora Pall., has exhibited a great hepatoprotective effect. AIM OF THIS STUDY We investigated the effect of JXHG on concanavalin A (ConA)-induced acute live injury in mice, and to elucidate its underlying molecular mechanisms. MATERIALS AND METHODS Jiangkanling Capsule (900 mg/kg), low-dose JXHG (LJXHG, 700 mg/kg), high-dose JXHG (HJXHG, 1400 mg/kg) were administered to mice by oral gavage daily for 20 days prior to a single intravenous injection of ConA (20 mg/kg). Liver injury was evaluated by measuring the serum levels of enzymes and cytokines as well as liver histological analysis. We also measured the hepatic expression of cytokines at mRNA levels and the proteins related to NF-κB and Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways. RESULT Our results showed that JXHG pretreatment significantly alleviated ConA-induced live injury as evidenced by decreased serum levels of glutamic-pyruvic transaminase (ALT) and glutamic oxalacetic transaminase (AST), and reduced hepatocyte apoptosis and mortality. Furthermore, JXHG was able to significantly reduce the serum levels of proinflammatory cytokines, down-regulate the mRNA expression of interleukin-6 (IL-6) and interferon-γ (IFN-γ), and up-regulate IL-10 as well as superoxide-dimutase-1 (SOD1), glutathione reductase (GSR) and Glutathione peroxidase 2 (GPX2) mRNA in the liver tissues after Con A injection. In addition, JXHG pretreatment dramatically suppressed the phosphorylation of NF-κB p65 (p65), increased Nrf2 expression, and decreased the expression ratio of cleaved caspase-3/caspase-3 in liver tissues. CONCLUSION These results suggest that JXHG protects against ConA-induced acute live injury through inhibiting NF-κB mediated inflammatory pathway and promoting Nrf2 mediated anti-oxidative stress signaling pathway.
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Affiliation(s)
- Huan-Huan Tang
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China; Department of Pharmacology, School of Pharmacy, Guilin Medical University, No. 109 Huanchengbei Road Two, Guilin 541004, China
| | - Hai-Long Li
- Infinitus R&D Center, Infinitus (China) Company Ltd, No.19, Sicheng Road, The First Floor of HongTai Zhihui Valley, Tianhe Area, Guangzhou 510663, China
| | - Yue-Xuan Li
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China
| | - Yan You
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China
| | - Yun-Yun Guan
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China
| | - Su-Lin Zhang
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China
| | - Li-Xin Liu
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China
| | - Wei-Lian Bao
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China
| | - Yong Zhou
- Infinitus R&D Center, Infinitus (China) Company Ltd, No.19, Sicheng Road, The First Floor of HongTai Zhihui Valley, Tianhe Area, Guangzhou 510663, China.
| | - Xiao-Yan Shen
- Department of Pharmacology, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China.
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Translational Advances of Hydrofection by Hydrodynamic Injection. Genes (Basel) 2018; 9:genes9030136. [PMID: 29494564 PMCID: PMC5867857 DOI: 10.3390/genes9030136] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Revised: 02/20/2018] [Accepted: 02/21/2018] [Indexed: 12/11/2022] Open
Abstract
Hydrodynamic gene delivery has proven to be a safe and efficient procedure for gene transfer, able to mediate, in murine model, therapeutic levels of proteins encoded by the transfected gene. In different disease models and targeting distinct organs, it has been demonstrated to revert the pathologic symptoms and signs. The therapeutic potential of hydrofection led different groups to work on the clinical translation of the procedure. In order to prevent the hemodynamic side effects derived from the rapid injection of a large volume, the conditions had to be moderated to make them compatible with its use in mid-size animal models such as rat, hamster and rabbit and large animals as dog, pig and primates. Despite the different approaches performed to adapt the conditions of gene delivery, the results obtained in any of these mid-size and large animals have been poorer than those obtained in murine model. Among these different strategies to reduce the volume employed, the most effective one has been to exclude the vasculature of the target organ and inject the solution directly. This procedure has permitted, by catheterization and surgical procedures in large animals, achieving protein expression levels in tissue close to those achieved in gold standard models. These promising results and the possibility of employing these strategies to transfer gene constructs able to edit genes, such as CRISPR, have renewed the clinical interest of this procedure of gene transfer. In order to translate the hydrodynamic gene delivery to human use, it is demanding the standardization of the procedure conditions and the molecular parameters of evaluation in order to be able to compare the results and establish a homogeneous manner of expressing the data obtained, as ‘classic’ drugs.
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MacGregor HL, Ohashi PS. Molecular Pathways: Evaluating the Potential for B7-H4 as an Immunoregulatory Target. Clin Cancer Res 2017; 23:2934-2941. [PMID: 28325750 DOI: 10.1158/1078-0432.ccr-15-2440] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 12/05/2016] [Accepted: 03/15/2017] [Indexed: 11/16/2022]
Abstract
With the clinical success of CTLA-4 and PD-1 blockade in treating malignancies, there is tremendous interest in finding new ways to augment antitumor responses by targeting other inhibitory molecules. In this review, we describe one such molecule. B7-H4, a member of the B7 family of immunoregulatory proteins, inhibits T cell proliferation and cytokine production through ligation of an unknown receptor expressed by activated T cells. Notably, B7-H4 protein expression is observed in a high proportion of patients' tumors across a wide variety of malignancies. This high expression by tumors in combination with its low or absent protein expression in normal tissues makes B7-H4 an attractive immunotherapeutic target. Preclinical investigation into B7-H4-specific chimeric antigen receptor (CAR) T cells, antibody-mediated blockade of B7-H4, and anti-B7-H4 drug conjugates has shown antitumor efficacy in mouse models. The first clinical trials have been completed to assess the safety and efficacy of a B7-H4 fusion protein in ameliorating rheumatoid arthritis. Clin Cancer Res; 23(12); 2934-41. ©2017 AACR.
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Affiliation(s)
- Heather L MacGregor
- Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.,Department of Immunology, University of Toronto, Toronto, Ontario, Canada
| | - Pamela S Ohashi
- Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. .,Department of Immunology, University of Toronto, Toronto, Ontario, Canada.,Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
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Yuan X, Li Y, Pan X, Peng X, Song G, Jiang W, Gao Q, Li M. IL-38 alleviates concanavalin A-induced liver injury in mice. Int Immunopharmacol 2016; 40:452-457. [PMID: 27723569 DOI: 10.1016/j.intimp.2016.09.023] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2016] [Revised: 09/20/2016] [Accepted: 09/23/2016] [Indexed: 12/23/2022]
Abstract
Interleukin (IL)-38 is a poorly characterized cytokine of the IL-1 family with anti-inflammatory activity. The role of IL-38 in liver injury remains unknown. We have investigated the potential effect of hydrodynamic-based gene delivery to express human IL-38 in mice with concanavalin A (Con A)-induced liver injury. Transfer of plasmid DNA encoding IL-38 significantly reduced hepatic toxicity and serum levels of aspartate aminotransferase and alanine aminotransferase compared with administration of a control plasmid. Moreover, IL-38 expression dramatically reduced serum levels of several pro-inflammatory cytokines, such as tumor necrosis factor-α, interferon-γ, IL-6, IL-17, and IL-22, but not levels of the anti-inflammatory cytokine IL-10. These results suggest that in vivo expression of human IL-38 in mice has hepatoprotective effects against Con A-induced liver injury by inhibition of inflammatory cytokine production.
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Affiliation(s)
- Xianli Yuan
- Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China
| | - Yan Li
- Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China
| | - Xiuhe Pan
- Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China
| | - Xiao Peng
- Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China
| | - Gaihuan Song
- Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China
| | - Wenwen Jiang
- Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China
| | - Qiaoyan Gao
- Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China
| | - Mingcai Li
- Department of Immunology, Ningbo University School of Medicine, Ningbo 315211, China.
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Hong B, Qian Y, Zhang H, Sang YW, Cheng LF, Wang Q, Gao S, Zheng M, Yao HP. Expression of B7-H4 and hepatitis B virus X in hepatitis B virus-related hepatocellular carcinoma. World J Gastroenterol 2016; 22:4538-4546. [PMID: 27182163 PMCID: PMC4858635 DOI: 10.3748/wjg.v22.i18.4538] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Revised: 02/27/2016] [Accepted: 03/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the expression and clinical significance of B7-H4 and hepatitis B virus X (HBx) protein in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC).
METHODS: The expression of B7-H4 in the human HCC cell lines HepG2 and HepG2.2.15 were detected by western blot, flow cytometry, and immunofluorescence. The expression of B7-H4 and HBx in 83 HBV-HCC was detected by immunohistochemistry, and the relationship with clinicopathological features was analyzed. Paraffin sections were generated from 83 HBV-HCC patients (22 females and 61 males) enrolled in this study. The age of these patients ranged from 35 to 77 years, with an average of 52.5 ± 11.3 years. All experiments were approved by the Ethics Committees of the Second Affiliated Hospital, Zhejiang University School of Medicine.
RESULTS: B7-H4 was significantly upregulated in HepG2.2.15 cells compared to HepG2 cells. Specifically, the protein expression of B7-H4 in the lysates of HepG2 cells was more than that in HepG2.2.15 cells. In addition, HBx was expressed only in HepG2.2.15 cells. Similar data were obtained by flow cytometry. The positive rates of B7-H4 and HBx in the tissues of 83 HBV-HCC patients were 68.67% (57/83) and 59.04% (49/83), respectively. The expression of HBx was correlated with tumor node metastases (TNM) stage, and the expression of B7-H4 was positively correlated with HBx (rs = 0.388; P < 0.01). The expression level of B7-H4 in HBx-positive HBV-HCC tissues was substantially higher than that in HBx-negative HBV-HCC tissues. The expression level of B7H4 was negatively related to tumor TNM stage.
CONCLUSION: Higher expression of HBx and B7-H4 was correlated with tumor progression of HBV-HCC, suggesting that B7-H4 may be involved in facilitating HBV-related hepatocarcinogenesis.
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Abstract
B7-H4 is a ligand in the B7 costimulatory family, executing suppressive function on the immune system in many diseases, such as cancer, allograft rejection, and autoimmune diseases. The receptor for this molecule has yet to be clarified. The engagement of B7-H4 inhibits proliferation of immune cells by stopping the cell cycle at the G0/G1 phase and leads to apoptosis via the Fas/FasL pathway consequently accelerating tumor progression and alleviating allograft rejection. The pathogenic role of B7-H4 in tumors has been widely established, but few studies have focused on its function in other disorders. Here, we review recent advances in our understanding of B7-H4 biology in disease settings other than tumors and document the beneficial values to treat those diseases by targeting this molecule and related signaling pathways.
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Decoy receptor 3 protects non-obese diabetic mice from autoimmune diabetes by regulating dendritic cell maturation and function. Mol Immunol 2010; 47:2552-62. [DOI: 10.1016/j.molimm.2010.07.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2010] [Revised: 07/04/2010] [Accepted: 07/05/2010] [Indexed: 12/31/2022]
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