Relationship between transforming growth factor β1 and anti-fibrotic effect of interleukin-10

Abstract

To study the effect of interleukin-10 (IL-10) on the expression of transforming growth factor beta1 (TGF-beta1) in hepatic fibrosis rats and the anti-fibrotic role of exogenous IL-10. Hepatic fibrosis was induced by carbon tetrachloride administered (CCl(4)) intraperitoneally. The experiment was performed in two stages. In the first stage, 60 SD rats were divided randomly into normal control group 1 (GN(1), n=8), hepatic fibrosis group (GC, n=28)and IL-10 intervened group (GI, n=24). At the beginning of the 7(th) and 11(th) wk, hepatic stellate cells (HSCs) were isolated, reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry were performed to detect the expression of TGF-beta1 in HSCs. Histological examination was used to determine the degree of hepatic fibrosis. In the second stage, 47 SD rats were divided randomly into normal control group 2 (GN(2), n=6)and CCl(4) group(GZ, n=41). At the end of the 9(th) wk, rats in GZ group were allocated randomly into model group(GM, n=9), IL-10 treatment group (GT, n=9)and recovered group (GR, n=9). At the end of the 12(th) wk, all rats were sacrificed. RT-PCR and immunohistochemistry were performed to detect the expression of TGF-beta1 in liver tissue. ELISA was used to assay serum TGF-beta1 levels. Hepatic fibrosis developed in rats with the increase of the injection frequency of CCl(4). In the first stage, hepatic fibrosis developed and HSCs were isolated successfully. At the 7(th) and 11(th) wk, TGF-beta1 mRNA in GC group increased significantly compared with that in GN(1) (P=0.001/0.042) and GI groups (P=0.001/0.007), whereas there was no significant difference between the two groups. The levels of TGF-beta1 at the beginning of the 7(th) wk was higher than that of the 11(th) wk (P=0.049). Immunocytochemistry results of TGF-beta1 were consistent with the above findings. In the second stage, TGF-beta1 increased significantly in GM group compared to GN(2). After treatment with IL-10, TGF-beta1 declined obviously. The expression of TGF-beta1 decreased in GR group but was still higher than that in GT group. The levels of TGF-beta1 are increased in hepatic fibrosis rats and decreased after treatment with exogenous IL-10. IL-10 may play an anti-fibrotic role by suppressing TGF-beta1 expression.