Starring role of toll-like receptor-4 activation in the gut-liver axis

Figure 2 Hepatic cell types express toll-like receptor-4. In the presence of the loss of lipopolysaccharides (LPS) tolerance, such as during non-alcoholic fatty liver disease, non-alcoholic steatohepatitis or HCV chronic hepatitis, TLR-4 is activated by gut-derived LPS and overexpressed. An altered balance of known miRNAs (miR155, miR21, let-7i) and chemokine receptors (CXCR4, CXCR7) could promote this condition. Then, activation and recruitment of inflammatory cells, ductular reaction and activation of endothelial and stellate cells drive liver inflammation and fibrosis. On the right, the mediators mainly involved in the fibrosis are presented (TGF-β, IGF-1, TNF-α, IL-6), on the left, mediators related to the inflammation are shown (TNF-α, IL-6, IL-1α, IL-8, GM-CSF, IFN-γ). TLR-4: Toll-like receptor-4; TNF-α: Tumor necrosis factor alpha; IL: Interleukin; GM-CSF: Granulocyte-macrophage colony-stimulating factor; IFN: Interferon; HCV: Hepatitis C virus; MMPs: Matrix metalloproteinases; NAFLD/NASH: Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.