Helicobacter hepaticus infection-induced IL-33 promotes hepatic inflammation and fibrosis through ST2 signaling pathways in BALB/c mice

肝幽门螺杆菌感染诱导的 IL-33 通过 ST2 信号通路促进 BALB/c 小鼠肝脏炎症和纤维化

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作者:Shuyang Cao, Liqi Zhu, Chen Zhu, Jie Feng, Jun Yin, Jin Lu, Yongliang Xu, Haitao Yang, Yuzheng Huang, Quan Zhang

Abstract

It has been documented that Helicobacter hepaticus (H. hepaticus) infection is linked to hepatic inflammation and fibrosis. Interleukin 33 (IL-33) is a cytokine involved in inflammatory and fibrotic diseases, but its relevance to H. hepaticus infection-induced liver inflammation and fibrosis is unknown. In this study, we found that the expression of IL-33 in mice liver was significantly induced by H. hepaticus infection at 24 weeks post infection (WPI). Immunohistochemistry analysis revealed that IL-33 was transferred from the nucleus to the cytoplasm due to infection. The quantitation of inflammatory cytokine and histopathology evaluation showed that IL-33 knockdown attenuated the H. hepaticus-induced hepatic inflammation and fibrosis. More importantly, H. hepaticus promoted the expression of the IL-33 receptor ST2 on cell surfaces, and the expression of ST2 then activated the expression nuclear factor-κB (p65), α-SMA, and Erk1/2. These observations provide novel insights into the pathogenic mechanism of hepatic inflammation and fibrosis during H. hepaticus infection.

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