Immunological aspects and therapeutic significance of an autoantibody against histone H1 in a rat model of concanavalin A-induced hepatitis.
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.
Nakano
Toshiaki
T
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
Goto
Shigeru
S
Lai
Chia-Yun
CY
Hsu
Li-Wen
LW
Takaoka
Yuki
Y
Kawamoto
Seiji
S
Chiang
Kuei-Chen
KC
Shimada
Yayoi
Y
Ohmori
Naoya
N
Goto
Takeshi
T
Sato
Shuji
S
Ono
Kazuhisa
K
Cheng
Yu-Fan
YF
Chen
Chao-Long
CL
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
D001323:Autoantibodies; D006657:Histones; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D003208:Concanavalin A; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin