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-beta(1) (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 microM acetaldehyde for 24h. The cells were then exposed to a medium containing 200 microM 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, 15min before acetaldehyde was added, did not present an increase in alpha(1)(I) collagen mRNA. These results show that PTX inhibits the expression of 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.
Hernández
E
E
Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, México, D.F. 09340, Mexico.
Correa
A
A
Bucio
L
L
Souza
V
V
Kershenobich
D
D
Gutiérrez-Ruiz
M C
MC
D000079:Acetaldehyde / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology* / Q000633:toxicity; D011347:Procollagen / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D024042:Collagen Type I; D015850:Interleukin-6; D011347:Procollagen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000079:Acetaldehyde; D010431:Pentoxifylline