Exp Mol Med.  1998 Jun;30(2):59-64.

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

• Lee KS
• Ryoo YW
• Song JY

Abstract

The equilibrium between deposition and degradation of extracellular matrix(ECM) is essential to normal tissue development 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-gamma (IFN-gamma) on stromelysin-1 gene expression in cultured human dermal fibroblasts. The steady-state levels of stromelysin-1 mRNA were increased in IFN-gamma treated cultured dermal fibroblasts. In the CAT assay, the stromelysin-1 promoter activity was increased 2.8-fold compared with untreated control. Therefore IFN-gamma stimulates the stromelysin-1 promoter activity, resulting in transcriptional enhancement of gene expression. Transforming growth factor-beta (TGF-beta) showed the antagonistic action to the effects of IFN-gamma in cultured dermal fibroblasts. Furthermore, gel mobility shift assays demonstrated enhanced AP-1 binding activities in nuclear extracts from cells incubated with IFN-gamma. These data suggest that IFN-gamma is an up-regulator and TGF-beta is a down regulator on the stromelysin-1 gene expression, respectively, and the AP-1 binding site may be necessary for gene response.

Keyword

stromelysin-1; interferon-g; AP-1; gene expression

MeSH Terms

Cell Nucleus
Cells, Cultured
Chloramphenicol O-Acetyltransferase/metabolism
Chloramphenicol O-Acetyltransferase/genetics
Collagenases/genetics
Collagenases/drug effects
Fibroblasts/metabolism
Fibroblasts/drug effects*
Gene Expression Regulation/drug effects
Human
Interferon Type II/pharmacology*
Promoter Regions (Genetics)
Recombinant Proteins/metabolism
Recombinant Proteins/genetics
Skin/cytology*
Stromelysin 1/metabolism*
Stromelysin 1/genetics*
Stromelysin 1/drug effects
Transcription Factor AP-1/metabolism
Transcription, Genetic
Transforming Growth Factor beta/pharmacology
Up-Regulation (Physiology)