title: Interferon- γ triggers hepatic stellate cell-mediated immune regulation through MEK/ERK signaling pathway.
abstract: Hepatic stellate cells (HSCs) interact with immune cells to actively participate in regulating immune response in the liver which is mediated by the effector molecules, including B7-H1. We demonstrated here that expression of B7-H1 on HSCs was markedly enhanced by interferon-(IFN-) γ stimulation. IFN- γ stimulated HSCs inhibited T-cell proliferation via induction of T-cell apoptosis (22.1% ± 1.6%). This immunosuppressive effect was inhibited by preincubation with an anti-B7-H1 antibody, or inhibitor of the MEK/ERK pathway inhibited IFN- γ mediated expression of B7-H1. Thus, regulation of B7-H1 expression on HSCs by IFN- γ represents an important mechanism that regulates immune responses in the liver favoring tolerogenicity rather than immunogenicity. Involvement of MEK/ERK pathway provides a novel target for therapeutic approaches.
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Gu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jianbin
authors.initials: J
authors.lastname: Xiang
authors.forename: Zongyou
authors.initials: Z
authors.lastname: Chen
authors.forename: Lianfu
authors.initials: L
authors.lastname: Wang
authors.forename: Lina
authors.initials: L
authors.lastname: Lu
authors.forename: Shiguang
authors.initials: S
authors.lastname: Qian
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017209:Apoptosis; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002867:Chromones / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D009025:Morpholines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: D000873:Anthracenes; D057134:Antibodies, Neutralizing; D060890:B7-H1 Antigen; D002867:Chromones; D009025:Morpholines; C432165:pyrazolanthrone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007371:Interferon-gamma; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3