Ann Dermatol.  1997 Apr;9(2):108-115. 10.5021/ad.1997.9.2.108.

The Effect of Interferon-γ 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-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.

Keyword

IL-4; TNF-α; IFN-γ; Type I collagen; Promoter activity

MeSH Terms

Animals
Blotting, Northern
Cats
Collagen
Collagen Type I
Cytokines
DNA, Complementary
Fibroblasts*
Gene Expression
Genes, Reporter
Humans*
Interleukin-4*
Necrosis*
RNA, Messenger
Skin*
Collagen
Collagen Type I
Cytokines
DNA, Complementary
Interleukin-4
RNA, Messenger
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