Pentoxifylline diminished acetaldehyde-induced collagen production in hepatic stellate cells by decreasing interleukin-6 expression

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-beta1 (IL-6 and TGF-beta(1)) in a rat hepatic stellate cell line (CFSC-2G) exposed to acetaldehyde was studied. CFSC-2G cells were treated with 175 AM acetaldehyde for 24 h. The cells were then exposed to a medium containing 200 muM 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 alpha(1)(I) collagen mRNA by 15%. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays of TGF-beta(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 alpha(1)(I) collagen mRNA. These results show that PTX inhibits the expression of a alpha(1)(I) collagen via the inhibition of IL-6 in acetaldehyde treated cells. The effect herein reported on IL-6 and alpha(1)(I) collagen mRNA adds to the previously described effect of PTX, which could be useful in the fibrogenic process induced by acetaldehyde. (C) 2002 Elsevier Science Ltd. All rights reserved.