Tumor necrosis factor, alpha-induced protein 8-like 2 (TIPE2) is associated with the development of hepatic inflammatory diseases. However, to date, the possible role of TIPE2 in autoimmune hepatitis (AIH) has not been reported. The present study aimed to investigate the expression of TIPE2 in peripheral blood mononuclear cells (PBMCs) of mice with AIH. Furthermore, the liver function, pro-inflammatory cytokine production and hepatic histopathology were examined in TIPE2-deficient mice in order to evaluate whether TIPE2 is involved in the pathogenesis of AIH. A murine model of AIH was induced by treatment with concanavalin A (ConA). The expression of TIPE family members in the PBMCs was examined using reverse-transcription quantitative polymerase chain reaction analysis, while the protein expression of TIPE2 was additionally detected by western blot analysis. The activity of alanine amiotransferase (ALT) and aspartate aminotransferase (AST) in the serum was measured on an automated chemical analyzer to assess liver function. The serum levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-12 were measured using commercial ELISA kits. Hematoxylin and eosin staining was performed to assess hepatic histopathology. The results showed that the expression of TIPE2 was significantly decreased in the mice with AIH. Following ConA-induced AIH, TIPE2-deficient mice had significantly increased serum ALT and AST levels, enhanced production of pro-inflammatory cytokines, as well as more severe hepatic inflammation compared with the wild-type mice. In conclusion, the present study demonstrated, for the first time, that TIPE2 is involved in the pathogenesis of AIH. TIPE2 prevents liver dysfunction and inhibits deleterious inflammatory immune responses after AIH and may therefore serve as a novel agent for the treatment of AIH.
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