IL-10 Inhibits Transforming Growth Factor-ß-Induction of Type I Collagen mRNA Expression via Both JNK and p38 Pathways in Human Lung Fibroblasts

Abstract

Transforming growth factor-ß (TGF-ß) is a key factor for understanding the pathogenesis of fibrotic disorders such as idiopathic pulmonary fibrosis (IPF). We have demonstrated that interleukin-10 (IL-10) suppresses TGF-ß-induced expression of type I collagen (COL1) mRNA in a human lung fibroblast cell line (WI-38). However, the inhibitory mechanism has not yet been clearly elucidated. Thus, in the current study, we investigate the effects of IL-10 blockade of TGF-ß signaling which regulates COL1 mRNA expression. In WI-38 cells, IL-10 inhibits TGF-ß-mediated phosphorylation of both, c-Jun HN2-terminal kinase (JNK) and p38, but does not suppress TGF-ß- mediated phosphorylation of Smad2 or affect TGF-ß-upregulation of Smad7 mRNA expression. In addition, SP600125 and SB203580, specific inhibitors of JNK and p38, respectively, attenuate TGF-ß-induced COL1 mRNA expression in WI-38 cells. These results suggest that IL-10 inhibits TGF-ß-induced COL1 mRNA expression via both JNK and p38 pathways but not Smad pathways in WI-38 cells. This inhibitory mechanism may provide a novel insight into therapeutic strategies for fibrotic disorders such as IPF.