Elsevier

Journal of Hepatology

Volume 27, Issue 6, December 1997, Pages 1067-1080
Journal of Hepatology

Effect of tumour necrosis factor-α on proliferation, activation and protein synthesis of rat hepatic stellate cells

https://doi.org/10.1016/S0168-8278(97)80151-1Get rights and content

Abstract

Background/Aims: Hepatic stellate cells represent the principal matrix-synthesising cells of damaged liver and are targets of a number of cytokines currently under investigation. The study analyses the effects of tumour necrosis factor-α and interferon-γ on proliferation, “activation” and protein synthesis of hepatic stellate cells.

Methods: Primary cultures of hepatic stellate cells were exposed to tumour necrosis factor-α and interferon-γ. Cell proliferation, was studied by 3H-thymidine and bromo-deoxy-uridine incorporation. Protein synthesis was analysed using immunoprecipitation, Western- and Northern blotting techniques.

Results: Proliferation of hepatic stellate cells was reduced by tumor necrosis factor-α and interferon-γ, while “activation” of hepatic stellate cells as assessed by expression of smooth muscle α-actin and of TGF-β/activin type I receptor was induced by tumour necrosis factor-α but downregulated by interferon-γ. Tumour necrosis factor-α increased the synthesis of distinct extracellular matrix proteins, particularly of fibronectin and tenascin, but decreased collagen type III expression. In contrast, interferon-γ reduced the synthesis of all connective tissue proteins tested. Among the protease inhibitors, interferon-γ induced C1-esterase inhibitor synthesis, while tumour necrosis factor-α stimulated plasminogen activator inhibitor type 1 production.

Conclusions: Tumour necrosis factor-α and interferon-γ decrease proliferation of hepatic stellate cells, while “activation” of hepatic stellate cells and synthesis of proteins involved in matrix metabolism are regulated in a differential, cytokine-specific manner, suggesting that both cytokines play an important role in liver repair.

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