The Effect of Interferon-r and Tumor Necrosis Factor-α on COL1A2 Promoter Activity Elevated by Interleukin-4 in Human Skin Fibroblasts Cultures

Abstract

Background: IL-4 is known as a potent stimulating factor and, TNF-a and IFN-r suppress collagen synthesis of dermal fibroblasts. However, relatively little is known about interaction of these cytokines. Objective: The purpose of this study was to evaluate the interactional effect of TNF-a and INF-r for the type I collagen gene expression and promoter activation produced by IL-4. Methods: Using dermal fibroblasts from the normal skin cultured with three cytokines, IL- 4, TNF-a and IFN-y, we examined Northern blot analysis with each cDNA and assayed CAT activity with human pro a 2(l)collagen(COL1A2)/CAT reporter gene chimeric construct. Results: Compared to the control, treating with IL-4 resulted in prominent elevation of both type I procollagen mRNA levels and prce 2(I) collagen promoter activity. IL-4 with TNF-a suppressed the IL-4 induced elevations, whereas IL-4 with IFN-r did not reveal the obvious suppression of the elevations produced by IL-4. Fibroolasts treated with IL-4 together with IFN-r and TNF-a completely abolished the type I procollagen gene expression and the activation of COL1A2 promoter gene elicited by IL-4. Conclusion: IL-4 induced enhancement of type I collagen gene expression was synergistically suppressed by TNF-a and IFN-r on transcriptional level.(Ann Dermatol 9:(2) 108-115, 1997).