Figure 10.

Proposed mechanism of the interaction between bile acids and the IL-23/IL-17A axis. Bile acids up-regulate MIP-2 and other cytokines in hepatocytes by an Egr-1–dependent mechanism. Bile acids also up-regulate IL-23 in hepatocytes through AKT and JNK activation. IL-23 maintains Th17 cellular expansion and promotes the production of IL-17A. Through an unknown signaling cascade, IL-17A synergistically enhances TCA-induced production of MIP-2 and IL-23 by hepatocytes. Enhanced production of IL-23 leads to the formation of a positive feedback loop, which further amplifies inflammation during cholestasis.