Effects of various cytokines on collagen synthesis by normal rat hepatocytes in primary cultures and fibroblasts.

Collagen formation is an important function of liver parenchymal and nonparenchymal cells that may be relevant to the pathogenesis of hepatic fibrosis. In the present study, the effect of various kinds of cytokines and prednisolone on collagen synthesis by hepatocytes obtained from perfused rat livers and confluent human skin fibroblasts were investigated. The cells were cultured in serum-free medium for 24 h with [3H]proline and various additives. The amounts of collagen and noncollagen protein synthesis were calculated from the incorporation of [3H]proline into collagen-sensitive and collagen-resistant proteins. The additions of interleukin 1 alpha, interleukin 1 beta and transforming growth factor alpha enhanced both collagen and noncollagen protein synthesis by hepatocytes as well as by fibroblasts. Transforming growth factor beta also increased both collagen and noncollagen protein synthesis by fibroblasts while it selectively inhibited collagen synthesis by hepatocytes. Interferon preparations and prednisolone showed a selective suppression of collagen synthesis by both cells, indicating that these additives did not affect either cell viability or proliferation during the observed period. These results suggest that collagen synthesis by liver parenchymal cells is either positively or negatively modulated by various kinds of cytokines and hormone.