Pathogenesis of Liver Fibrosis: Modulation of Stellate Cells by Chemokines

Liver fibrosis is the common sequel of chronic liver diseases and is associated with high morbidity and mortality in affected patients. In recent years, the contribution of chemokines and their receptors to liver fibrosis has been delineated. Chemokines are a family of chemotactic and immunomodulatory molecules that act through different G-protein coupled receptors on target cells. Apart from their classical function of regulating immune cell recruitment during chronic liver injury, chemokines can directly affect the function of hepatic stellate cells within the liver. Up to now, nine of the 19 known chemokine receptors have been characterised on stellate cells. Stimulation of most of these receptors with specific ligands leads to increased migration and proliferation of stellate cells, suggesting predominantly profibrotic effects of chemokines. The only chemokine receptor with potential antifibrotic effects identified so far is CXCR3. Notably, hepatic stellate cells are not only a target but also a source of chemokines which contributes to the direct interaction between stellate cells and other cells during fibrogenesis. The further characterisation of this interaction will yield new therapeutic options for the treatment of chronic liver diseases. In this respect chemokines are a valuable target as oral chemokine receptor antagonists have already been licensed for human use.