Chemokines in liver inflammation and fibrosis

Chemokines may be involved in the tissue response to injury regulating the influx of leukocytes, and modulating a number of other critical biologic actions, including angiogenesis, neoplastic growth, myo-fibroblast activation, and the response to viral infections. In the liver, up-regulated expression of different members of the chemokine system may be induced by almost all types of injury, and there is often a clear relation between the chemokine pattern activated by different types of injury and the predominant subclasses of leukocytes which infiltrate the liver. Neutralization of specific chemokines by passive immunization or the use of animals deficient in specific chemokines or chemokine receptors has indicated a causal relation between up-regulation of chemokines and leukocyte infiltration. Inflammation is part of the liver wound healing response, that in chronic conditions leads to the development of fibrosis and cirrhosis. Hepatic stellate cells, which play a leading role in the development of fibrosis following their transition to myofibroblasts, express different chemokines. Chemokine expression by stellate cells is regulated by soluble mediators, in particular pro-inflammatory cytokines, as well as growth factors, proteases, and products of oxidative stress. In addition, stellate cells also respond to chemokines with biologic actions relevant for tissue repair, such as cell migration or induction of other chemokines. These data indicate that chemokines in the liver may modulate the progression of liver fibrosis through actions on hepatic stellate cells.