2024-03-29T12:38:15Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/846992022-11-17T02:08:08Zhdl_2115_20044hdl_2115_124Pivotal Role of Signal-Transducing Adaptor Protein-2 in Pathogenesis of Autoimmune HepatitisSasaki, YutoSaitoh, KodaiKagohashi, KotaKitai, YuichiMuromoto, RyutaOritani, KenjiKashiwakura, Jun-IchiMatsuda, Tadashisignal-transducing adaptor protein-2autoimmune hepatitisinterferon-γ (IFN-γ)Fas ligand (FasL)caspase-3464Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein involved in inflammatory and immune responses, such as inflammatory bowel disease and allergic responses. In this study, we investigated the role of STAP-2 in the pathogenesis of autoimmune hepatitis. After intravenous injection of concanavalin A (ConA), STAP-2 knock out (KO) mice showed more severe liver necrosis along with substantial lymphocyte infiltration compared to wild type (WT) mice. Serum alanine aminotransferase levels were significantly higher in ConA-injected STAP-2 KO mice than in WT mice. Levels of interferon-gamma (IFN-gamma), an important factor for liver necrosis, were also significantly increased in sera of STAP-2 KO mice compared to WT mice after ConA injection. Statistically significant upregulation of Fas ligand (FasL) expression was observed in the livers of ConA-injected STAP-2 KO mice compared to WT mice. In accordance with these results, apoptotic signals were facilitated in STAP-2 KO mice compared to WT mice after ConA injection. Correctively, these results suggest that STAP-2 is involved in the pathogenesis of autoimmune hepatitis by regulating the expression of FasL and the production of IFN-gamma.The Pharmaceutical Society of JapanJournal Articlehttp://hdl.handle.net/2115/846990918-61581347-5215Biological & pharmaceutical bulletin4412189819012021-12-01enginfo:doi/10.1248/bpb.b21-00595none