title: Immunological aspects and therapeutic significance of an autoantibody against histone H1 in a rat model of concanavalin A-induced hepatitis.
abstract: We previously demonstrated the immunosuppressive activity of anti-histone H1 autoantibody induced in experimental and clinical liver allograft tolerance. This study aimed to explore the immunological aspects of anti-histone H1 autoantibody in liver injury induced by concanavalin A (Con A). To establish a Con A-hepatitis model, 20 mg/kg Con A was intravenously injected into rats, after which liver function and histopathological analyses were performed. In this model, anti-histone H1 autoantibody was transiently induced in the sera during the natural recovery stage, 3-7 days after Con A injection. To evaluate the therapeutic significance of anti-histone H1 autoantibody, a polyclonal antibody against histone H1 was intraperitoneally injected immediately after Con A injection. We found that injection of anti-histone H1 antibody could reduce Con A-induced liver damage. Further mechanical analyses revealed that anti-histone H1 antibody altered the intracellular activation of mitogen-activated protein kinase, nuclear factor-kappaB and calcineurin via T-cell receptor signalling, suggesting that anti-histone H1 antibody may protect the liver from Con A-induced injury by inhibiting activation of effector T cells. These findings suggest that anti-histone H1 autoantibody may be a natural immune regulatory factor that protects inflamed livers suffering from autoimmune hepatitis and may lead to T-cell unresponsiveness through the selective regulation of mitogen-activated protein kinase/nuclear factor-kappaB and calcineurin signalling.
authors.affiliation: Liver Transplantation Program and Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Centre, Chang Gung University College of Medicine, Niao-Sung, Kaohsiung, Taiwan. toshi.nakano@msa.hinet.net
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakano
authors.forename: Shigeru
authors.initials: S
authors.lastname: Goto
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lai
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Hsu
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takaoka
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Kuei-Chen
authors.initials: KC
authors.lastname: Chiang
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Shimada
authors.forename: Naoya
authors.initials: N
authors.lastname: Ohmori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Goto
authors.forename: Shuji
authors.initials: S
authors.lastname: Sato
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ono
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Cheng
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000627:therapeutic use*; D019703:Calcineurin / Q000276:immunology / Q000378:metabolism; D003208:Concanavalin A / Q000009:adverse effects / Q000276:immunology*; D004195:Disease Models, Animal; D019693:Hepatitis, Autoimmune / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006657:Histones / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction / Q000276:immunology
chemical_list: D001323:Autoantibodies; D006657:Histones; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D003208:Concanavalin A; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin