Cytokines and fibrogenesis.
Cytokines play a major role in the development of hepatic fibrosis, the wound-healing response of the liver to chronic injury. Major concepts in defining the role of cytokines in fibrogenesis include (1) Cytokines may be pro- or antifibrogenic; (2) autocrine, paracrine, and matrix-bound sources of cytokines are the most important; and (3) multiple mechanisms of cytokine regulation are essential to fine-tune their effects. The hepatic stellate cell is the key effector of the fibrotic response and both a principal source and target of cytokines. Activation of stellate cells connotes the conversion of a resting vitamin A-rich cell to one which is proliferative, contractile, fibrogenic, and devoid of vitamin A. The features of stellate cell activation provide a framework in which to understand how cytokines drive fibrosis. These features include (1) proliferation; (2) contractility; (3) fibrogenesis; (4) extracellular matrix degradation; (5) chemotaxis; (6) cytokine release; and (7) retinoid loss. The insights gained from illuminating the role of stellate cells has engendered realistic hopes for treating hepatic fibrosis through modulation of cytokine actions.
Friedman
S L
SL
Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
D017667:Adipocytes / Q000502:physiology; D000818:Animals; D016207:Cytokines / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism; D008115:Liver Regeneration
D016207:Cytokines