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.

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.

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.

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.

IL-4 induced enhancement of type I collagen gene expression was synergistically suppressed by TNF-α and IFN-γ on transcriptional level.