Toll‐like receptors in alcoholic liver disease, non‐alcoholic steatohepatitis and carcinogenesis

Activation of innate immune systems including Toll‐like receptor ( TLR ) signaling is a key in chronic liver disease. Recent studies suggest that gut microflora‐derived bacterial products (i.e. lipopolysaccharide [ LPS ], bacterial DNA ) and endogenous substances (i.e. high‐mobility group protein B1 [ HMGB 1], free fatty acids) released from damaged cells activate hepatic TLR s that contribute to the development of alcoholic ( ASH ) and non‐alcoholic steatohepatitis ( NASH ) and liver fibrosis. The crucial role of TLR 4, a receptor for LPS , has been implicated in the development of ASH , NASH , liver fibrosis, and hepatocellular carcinoma. However, the role of other TLR s, such as TLR 2 and TLR 9 in chronic liver disease remains less clear. In this review, we will discuss the role of TLR 2, 4, and 9 in K upffer cells and hepatic stellate cells in the development of ASH , NASH , and hepatocarcinogenesis.