Mast cell tryptase does not alter matrix metalloproteinase expression in human dermal fibroblasts: Further evidence that proteolytically-active tryptase is a potent fibrogenic factor

There is compelling in vitro and in vivo evidence to implicate mast cells i n the development of fibrosis. However, an important question remains as to the mechanisms by which mast cells mediate fibrosis. Recent evidence from our laboratory (Gruber et at., 1997, J. Immunol., 158:2370-2317) has reveal ed that tryptase, the unique and abundant serine protease of human mast cel ls, is capable of activating fibroblasts by stimulating chemotaxis, prolife ration, and procollagen mRNA synthesis. Regulation of matrix metalloprotein ase (MMP) expression is another key step in connective tissue remodeling. T herefore, the effect of tryptase on fibroblast MMP expression was investiga ted. Proteolytically active tryptase did not alter the cellular mRNA levels for fibroblast MMP-1, MMP-2, MMP-3, and MMP-9 as detected by RNase protect ion assays. Moreover, tryptase did not alter the basal levels of MMP-1, MMP -2, MMP-3, MMP-9, or the tissue inhibitor of MMP-1 (TIMP-1) in fibroblast c onditioned media as detected by specific enzyme-linked immunosorbent assay (ELISA). These results indicate that tryptase does not increase MMP express ion in normal dermal fibroblasts. Moreover, these data strengthen the poten tial role of this unique serine protease as a potent fibrogenic factor. (C) 1999 Wiley-Liss, inc.