PENTOXIFYLLINE DIMINISHED ACETALDEHYDE-INDUCED COLLAGEN PRODUCTION IN HEPATIC STELLATE CELLS BY DECREASING INTERLEUKIN-6 EXPRESSION

• Published in: Pharmacological research 2002-11, Vol.46 (5), p.435-443
• Main Authors: HERNÁNDEZ, E., CORREA, A., BUCIO, L., SOUZA, V., KERSHENOBICH, D., GUTIÉRREZ-RUIZ, M.C.
• Format: Article
• Language: English
• Subjects: acetaldehyde; Acetaldehyde - pharmacology; Animals; Blotting, Northern; Cell Line; Cell Survival - drug effects; collagen; Collagen Type I - secretion; hepatic stellate cells; IL-6; Interleukin-6 - biosynthesis; Liver - cytology; Liver - drug effects; Liver - metabolism; pentoxifylline; Pentoxifylline - pharmacology; Pentoxifylline - toxicity; Procollagen - secretion; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Transforming Growth Factor beta - biosynthesis
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/S1043661802002025

The effect of pentoxifylline (PTX), a methylxanthine derivative, on collagen induction and secretion and on the production of mRNA of two fibrogenic cytokines: interleukin-6 and transforming growth factor- β 1 (IL-6 and TGF- β 1) in a rat hepatic stellate cell line (CFSC-2G) exposed to acetaldehyde was studied. CFSC-2G cells were treated with 175 μM acetaldehyde for 24 h. The cells were then exposed to a medium containing 200 μM PTX. Collagen secretion, increased 2.6 times in acetaldehyde treated cells. Cells exposed to acetaldehyde and treated with PTX diminished collagen secretion to control values and decreased α 1(I) collagen mRNA by 15%. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays of TGF- β 1 mRNA showed no variation in different experimental conditions. However, PTX induced a decrease of 32% in IL-6 mRNA in acetaldehyde-treated cells. CFSC-2G cells treated with anti-IL-6 monoclonal antibody, 15 min before acetaldehyde was added, did not present an increase in α 1(I) collagen mRNA. These results show that PTX inhibits the expression of α 1(I) collagen via the inhibition of IL-6 in acetaldehyde treated cells. The effect herein reported on IL-6 and α 1(I) collagen mRNA adds to the previously described effect of PTX, which could be useful in the fibrogenic process induced by acetaldehyde.