Figure 7.

TLR4 signaling in alcoholic steatohepatitis and fibrosis. Excessive alcohol abuse induces changes in the composition of intestinal microbiota and bacterial overgrowth. With tight junction disintegrity, intestinal permeability increases, causing the translocation of gut microflora-derived LPS into the liver through the portal vein. Translocated LPS activates TLR4 on both Kupffer cells and HSCs. TLR4 signaling induces the production of chemokines that promote migration of Kupffer cells and HSCs. The TLR4–TRIF–IRF3 pathway and miR-155 control TLR4 activation in Kupffer cells. These events induce liver inflammation, hepatocyte steatosis, and fibrosis.