Figure 2

Signalling pathways triggered by TLR4 activation as a result of damage to the portal system. Altered barrier function resulting in increased bacterial translocation allows bacterial products including lipopolysaccharide (LPS) to activate hepatic stellate cells (HSCs) through Toll-like receptors (TLRs) (TLR4 shown as an example TLR). Activation of TLR4 through LPS binding initiates numerous signalling cascades which culminate in activation of transcription factors NF-κB and AP-1 and production of inflammatory cytokines/chemokines and immune mediators. This activation sensitises HSCs to the effects of transforming growth factor TGF-β which ultimately results in HSC activation and increased extracellular matrix/collagen production resulting in increased hepatic fibrosis.