Matrix metalloproteinases-2 and-9 are secreted from human fibroblasts

To investigate the pathophysiological role of fibroblasts in tissue metabolism, we analysed gelatin-degrading enzymes secreted from skin cells in culture. Using a gelatin-zymography method, matrix metalloproteinase (MMP)-2 was constitutively secreted from fibroblasts, whereas both MMP-2 and MMP-9 were secreted from keratinocytes. MMP-9 expression by fibroblasts was induced by the addition of transforming growth factor (TGF)-beta1 or tumour necrosis factor (TNF)-alpha to the cultures. Moreover, TGF-beta1, TNF-alpha, or epidermal growth factor augmented the secretion of MMP-2 from fibroblasts. These results indicate that MMP-9 together with MMP-2 secreted from fibroblasts could play important roles in tissue metabolism, including cytokine-induced inflammation.