Interferon-γ upregulates the stromelysin-1 gene expression by human skin fibroblasts in culture

Abstract

The equilibrium between deposition and degradation of extracellular matrix (ECM) is essential to normal tissue developement and repair of wound or inflammatory responses. It has recently become apparent that several cytokines and growth factors are capable of modulating fibroblast proliferation and biosynthetic activity. To understand the role of these factors in connective tissue regulation, we examined the effect of interferon-γ (IFN-γ) on stromelysin-1 gene expression in cultured human dermal fibroblasts. The steady-state levels of stromelysin-1 mRNA were increased in IFN-γ treated cultured dermal fibroblasts. In the CAT assay, the stromelysin-1 promoter activity was increased 2.8-fold compared with untreated control. Therfore IFN-γ stimulates the stromelysin-1 promoter activity, resulting in transcriptional enhancement of gene expression. Transforming growth factor-β (TGF-β) showed the antagonistic action to the effects of lFN-γ in cultured dermal fibroblasts. Furthermore, gel mobility shift assays demonstrated enhanced AP-1 binding activities in nuclear extracts from cells incubated with IFN-γ. These data suggest that IFN-1, is an up-regulator and TGF-β is a down regulator on the stromelysin-1 gene expression, respectively, and the AP-1 binding site may be necessary for gene response.