Protection against liver injury by PGE1 or anti-TNF-alpha is associated with a reduction of TNF-R1 expression in hepatocytes.
BACKGROUND: Tumour necrosis factor-alpha (TNF-5) has been shown to exacerbate or protect against liver injury in different experimental models. In a previous study, we observed that enhancement of TNF-alpha expression in hepatocytes by prostaglandin E1 (PGE1) pre-administration induced iNOS expression and cytoprotection against experimental liver injury in rats. Nevertheless, the reduction of TNF-alpha bioactivity by anti-TNF-alpha antibodies also reduced liver injury by D-GalN. The purpose of the present study was to evaluate whether protection by PGE1 or anti-TNF-alpha was related to a common effect on the membrane-bound TNF-alpha receptor expression. METHODS: Liver injury was induced in male Wistar rats by intraperitoneal injection of D-galactosamine (D-GalN) (1 g/kg). PGE1 or anti-TNF-alpha was administered at 30 or 60 min before D-GalN, respectively. Liver injury was evaluated by alanine aminotransferase (ALT) activity in serum and histological examination in liver sections. TNF-alpha was determined by ELISA in serum. The expression of TNF-alpha receptor type 1 (TNF-R1) and TNF-alpha receptor type 2 (TNF-R2) in hepatocytes was assessed by immunohistochemistry and immunoprecipitation + Western-blot analysis. RESULTS: PGE1 or anti-TNF-alpha reduced liver injury induced by D-GalN. Although PGE1 enhanced and anti-TNF-alpha reduced TNF-alpha concentration in serum, both protective treatments reduced the expression of TNF-R1 in hepatocytes. TNF-R2 was not detected in our experimental conditions. CONCLUSIONS: Our study showed that reduction of liver injury by PGE1 or anti-TNF-alpha antibodies was related to a reduction of TNF-R1 expression in hepatocytes.[1]References
- Protection against liver injury by PGE1 or anti-TNF-alpha is associated with a reduction of TNF-R1 expression in hepatocytes. Lozano, J.M., Collado, J.A., Medina, T., Muntané, J. Scand. J. Gastroenterol. (2003) [Pubmed]
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