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TGF-β and TNF-α stimulate MMP-9 production in murine epidermal keratinocytes

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Matrix metalloproteinases 2 and 9 (MMP-2 and -9) are zinc-dependent metalloenzymes and have gelatin-degrading activity. Both MMP are known to be secreted by many types of cells and play important roles in several biological changes including tissue remodeling and wound healing. In the present study, a primary culture of murine epidermal keratinocytes was prepared and effects of transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) on expression of MMP-2 and MMP-9 by the keratinocytes was examined. Gelatin zymography revealed that murine epidermal keratinocytes secreted proenzyme forms of MMP-2 and MMP-9, but the active forms of both MMP were hardly detectable, indicating that in vitro autoactivation of these proenzymes did not occur. Both TGF-β and TNF-α stimulated MMP-9 production in a dose-dependent manner, but the MMP-2 level was not changed. Interferon-γ hardly affected production of MMP-2 or MMP-9. Ribonuclease protection assay demonstrated that TNF-α increased the level of MMP-9 mRNA 6-fold compared to the control, whereas TGF-β slightly up-regulated it. These results suggest that expression of MMP-9 could be regulated by several cytokines in murine epidermal keratinocytes.
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Keywords: epidermal keratinocyte; matrix metalloproteinase; mouse; transforming growth factor-β; tumor necrosis factor-α

Document Type: Research Article

Affiliations: Department of Tissue Physiology, Tokyo University of Agriculture and Technology, Fuchu-shi, Japan

Publication date: June 1, 2003

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