Helicobacter hepaticus infection induces chronic hepatitis and fibrosis in male BALB/c mice via the activation of NF‐κB, Stat3, and MAPK signaling pathways.

Background: It has been documented that Helicobacter hepaticus (H hepaticus) infection is linked to chronic hepatitis and liver cancer. However, our understanding of the molecular mechanisms underlying progression of the H hepaticus‐induced hepatic inflammation to cellular hepatocarcinoma is still limited. Materials and methods: In our study, male BALB/c mice were infected by H hepaticus for 8, 12, 16, 20, and 24 weeks. Histopathology, H hepaticus colonization dynamics, select signaling pathways, and expression of key inflammatory cytokines in the liver were examined. Results: We found that H hepaticus was detectible in feces of mice at 7 days postinfection (DPI) by PCR, but it was not detected in the livers by PCR until 8 weeks postinfection (WPI). In addition, abundance of colonic and hepatic H hepaticus was progressively increased over the infection duration. H hepaticus‐induced hepatic inflammation and fibrosis were aggravated over the infection duration, and necrosis or cirrhosis developed in the infected liver at 24 WPI H hepaticus infection increased levels of alanine aminotransferase and aspartate aminotransferase. Moreover, mRNA levels of Il‐6 and Tnf‐α were significantly elevated in the livers of H hepaticus‐infected mice compared to uninfected control from 8 WPI to 24 WPI. Furthermore, Stat3, nuclear factor‐κB (p65), and MAPK (Erk1/2 and p38) were activated by H hepaticus infection. Conclusions: These data demonstrated that male BALB/c mice can be used as a new mouse model of H hepaticus‐induced liver diseases and that the H hepaticus‐induced liver injury is triggered by NF‐κB, Jak‐Stat, and MAPK signaling pathways. [ABSTRACT FROM AUTHOR]