title: Mast cell tryptase does not alter matrix metalloproteinase expression in human dermal fibroblasts: further evidence that proteolytically-active tryptase is a potent fibrogenic factor.
abstract: There is compelling in vitro and in vivo evidence to implicate mast cells in 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 al., 1997, J. Immunol. , 158:2310-2317) has revealed that tryptase, the unique and abundant serine protease of human mast cells, is capable of activating fibroblasts by stimulating chemotaxis, proliferation, and procollagen mRNA synthesis. Regulation of matrix metalloproteinase (MMP) expression is another key step in connective tissue remodeling. Therefore, the effect of tryptase on fibroblast MMP expression was investigated. 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 protection 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 conditioned media as detected by specific enzyme-linked immunosorbent assay (ELISA). These results indicate that tryptase does not increase MMP expression in normal dermal fibroblasts. Moreover, these data strengthen the potential role of this unique serine protease as a potent fibrogenic factor.
authors.affiliation: Department of Medicine, State University of New York at Stony Brook, Stony Brook, New York, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: B L
authors.initials: BL
authors.lastname: Gruber
authors.forename: M J
authors.initials: MJ
authors.lastname: Marchese
authors.forename: S
authors.initials: S
authors.lastname: Zucker
authors.forename: L B
authors.initials: LB
authors.lastname: Schwartz
authors.forename: R R
authors.initials: RR
authors.lastname: Kew
mesh_terms: D000328:Adult; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D053818:Chymases; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000201:enzymology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008934:Mitogens / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D012697:Serine Endopeptidases / Q000302:isolation & purification / Q000494:pharmacology*; D012867:Skin / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053802:Tryptases
chemical_list: D017077:Culture Media, Conditioned; D008934:Mitogens; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D000001:Calcimycin; D006493:Heparin; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D013755:Tetradecanoylphorbol Acetate