Toll-Like Receptor 7-Mediated Type I Interferon Signaling Prevents Cholestasis- and Hepatotoxin-Induced Liver Fibrosis

• DOI: 10.1002/hep.26981
• Publication Date: 2013-12-21T05:48:51Z
• Authors: Yoon Seok Roh; Surim Park; Jong Won Kim; Chae Woong Lim; Ekihiro Seki; Bumseok Kim
• Keywords: Hepatotoxin; IRF3

Toll-like receptor 7 (TLR7) signaling predominantly regulates production of type I interferons (IFNs), which has been suggested in clinical studies to be antifibrotic. However, the mechanistic role TLR7-type IFN axis liver fibrosis not elucidated. In present study, was induced wild-type (WT), TLR7-deficient, and IFN-α/β receptor-1 (IFNAR1)-deficient mice TLR7-mediated assessed cells isolated from these mice. TLR7-deficient IFNAR1-deficient were more susceptible than WT mice, indicating that exerts a protective effect against fibrosis. Notably, hepatic expression interleukin-1 antagonist (IL-1ra) suppressed TLR7- or compared with respective treatment recombinant IL-1ra reduced vivo activation TLR7 significantly increased IFNa4 liver. Interestingly, each cytokine had different cellular source, showing dendritic (DCs) are responsible cell for IFN, while Kupffer (KCs) mainly produce response IFN. Furthermore, by R848 injection proinflammatory cytokines, effects dependent on signaling. Consistent data, IFN-α primary KCs. Conclusion : activates DCs turn induces antifibrogenic Thus, manipulation IFN-IL-1ra may new therapeutic strategy (Hepatology 2014;60:237–249)