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

• Published in: Biochemical and biophysical research communications 2020-05, Vol.525 (3), p.654-661
• Main Authors: Cao, Shuyang, Zhu, Liqi, Zhu, Chen, Feng, Jie, Yin, Jun, Lu, Jin, Xu, Yongliang, Yang, Haitao, Huang, Yuzheng, Zhang, Quan
• Format: Article
• Language: English
• Subjects: Helicobacter hepaticus; IL-33; Inflammation; Liver fibrosis; ST2
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.02.139

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. •The mRNA and protein levels of IL-33 were elevated with Helicobacter hepatitis infection.•IL-33 transferred from the nucleus to the cytoplasm upon Helicobacter hepaticus infection.•H. hepaticus infection elicited hepatic inflammation and fibrosis via the IL-33/ST2 signaling pathway.