IL-4 and IL-13 induce type I collagen gene activity via the JNK signaling pathway in human fibroblasts. (94.28)

Abstract

Abstract Little is understood of the molecular mechanisms by which fibrotic diseases such as in Scleroderma, are manifested by interleukins (IL) 4 and 13. Studies support a role for the JNK signaling pathway via transcription factors c-Jun and ATF2, being involved in activating the collagen promoter and translation of the collagen gene. To examine the role of JNK signaling in IL-4/IL-13-induced collagen gene activation, we transfected human fibroblasts with a luciferase reporter plasmid under control of the α2(I) collagen promoter to assess JNK signaling on type I collagen promoter activity. We reveal a critical role for JNK 1 in IL-4/IL-13-induced collagen promoter activity subsequent to ectopic expression of c-Jun and ATF2. In contrast, introduction of a dominant negative (dn) mutant reduces basal and cytokine-induced promoter activity. We demonstrate that the JNK signaling pathway leading to the activation of the collagen gene in fibroblasts is effective not only for TGF-β signaling but also for IL-4/IL-13 signaling.