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

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-alpha and interferon-gamma on proliferation, "activation" and protein synthesis of hepatic stellate cells.

METHODS:

Primary cultures of hepatic stellate cells were exposed to tumour necrosis factor-alpha and interferon-gamma. 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-alpha and interferon-gamma, while "activation" of hepatic stellate cells as assessed by expression of smooth muscle alpha-actin and of TGF-beta/activin type I receptor was induced by tumour necrosis factor-alpha but downregulated by interferon-gamma. Tumour necrosis factor-alpha increased the synthesis of distinct extracellular matrix proteins, particularly of fibronectin and tenascin, but decreased collagen type III expression. In contrast, interferon-gamma reduced the synthesis of all connective tissue proteins tested. Among the protease inhibitors, interferon-gamma induced C1-esterase inhibitor synthesis, while tumour necrosis factor-alpha stimulated plasminogen activator inhibitor type 1 production.

CONCLUSIONS:

Tumour necrosis factor-alpha and interferon-gamma 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.

• Authors: T Knittel, L Müller, B Saile, G Ramadori
• Journal: Journal of hepatology (J Hepatol) Vol. 27 Issue 6 Pg. 1067-80 (Dec 1997) ISSN: 0168-8278 [Print] Netherlands
• PMID: 9453433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Extracellular Matrix Proteins
• Protease Inhibitors
• Tumor Necrosis Factor-alpha
• Interferon-gamma

Topics

• Adipocytes (drug effects, metabolism)
• Animals
• Cell Division (drug effects)
• Extracellular Matrix Proteins (biosynthesis)
• Interferon-gamma (pharmacology)
• Liver (cytology, drug effects)
• Protease Inhibitors (metabolism)
• Rabbits
• Rats
• Rats, Wistar
• Tumor Necrosis Factor-alpha (pharmacology)