Toll-like receptor signaling in liver regeneration, fibrosis and carcinogenesis.

Toll-like receptors (TLR) are the germline-coded pattern recognition receptors that sense microbial products. This signaling orchestrates complex signaling pathways that induce expression of inflammatory genes for host defense against invading microorganisms. Recent studies illustrate the role of TLR on non-infectious inflammatory diseases. The liver has a unique anatomy bridging with the intestine by portal vein and bile ducts. This allows delivery of products from intestinal microflora directly into the liver. Subsequently, microbial products cause acute and chronic inflammation through TLR signaling in the liver. Not only exogenous products, but endogenous denatured products released from dying cells also facilitate inflammation even in sterile conditions. Consequently, these responses elicit tissue repairing including liver regeneration and fibrogenesis. An aberrant regenerative response may lead to hepatic carcinogenesis. In this review, we highlight the recently accumulated knowledge about TLR signaling in liver regeneration, fibrosis and carcinogenesis.