Chemokines and Chemokine Receptors in the Development of NAFLD

Chemokines are chemo-attractants for leukocyte trafficking, growth, and activation in injured and inflammatory tissues. The chemokine system is comprised of 50 chemokine ligands and 20 cognate chemokine receptors. In the context of liver diseases, leukocytes, hepatocytes, hepatic stellate cells, endothelial cells, and vascular smooth muscle cells are capable of producing chemokines. Chemokine receptors are typically expressed in various leukocyte subsets. Given that inflammation is a critical factor for the transition from simple steatosis to non-alcoholic steatohepatitis (NASH), and fibrosis, the chemokine system may play a prominent role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Indeed, accumulating evidence shows elevated expression of chemokines and their receptors in the livers of obese patients with advanced steatosis and NASH. This chapter will discuss the underlying molecular mechanisms and the therapeutic potential of the chemokine systems in the pathogenesis of NAFLD. Among chemokines, we will highlight CCL2, CCL5, CXCL8-10, CX3CL1, and CXCL16 as pivotal mediators in the development of steatosis, NASH, and fibrosis.