The Effect of Interferon-γ and Tumor Necrosis Factor-α on COL1A2 Promoter Activity Elevated by Interleukin-4 in Human Skin Fibroblasts Cultures.
10.5021/ad.1997.9.2.108
- Author:
Dong Seok KIM
;
Sang Won KIM
;
Kyu Suk LEE
- Publication Type:Original Article
- Keywords:
IL-4;
TNF-α;
IFN-γ;
Type I collagen;
Promoter activity
- MeSH:
Animals;
Blotting, Northern;
Cats;
Collagen;
Collagen Type I;
Cytokines;
DNA, Complementary;
Fibroblasts*;
Gene Expression;
Genes, Reporter;
Humans*;
Interleukin-4*;
Necrosis*;
RNA, Messenger;
Skin*
- From:Annals of Dermatology
1997;9(2):108-115
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: IL-4 is known as a potent stimulating factor and, TNF-α and IFN-γ 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-α 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-α and IFN-γ, 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-α suppressed the IL-4 induced elevations, whereas IL-4 with IFN-γ did not reveal the obvious suppression of the elevations produced by IL-4. Fibroolasts treated with IL-4 together with IFN-γ and TNF-α 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-α and IFN-γ on transcriptional level.