title: Inactivation of tissue inhibitor of metalloproteinases by neutrophil elastase and other serine proteinases.
abstract: Tissue inhibitor of metalloproteinases (TIMP) from cultured bovine dental pulp inhibits human rheumatoid synovial matrix metalloproteinase 3 (MMP-3) with a stoichiometry of 1:1 on a molar basis. Among the serine proteinases examined, human neutrophil elastase, trypsin and alpha-chymotrypsin destroyed the inhibitory activity of TIMP against MMP-3 by degrading the inhibitor molecule into small fragments. In contrast, the inhibitory activity of TIMP was not significantly reduced by the actions of cathepsin G, pancreatic elastase and plasmin. These data indicate that neutrophils which infiltrate tissues in various inflammatory conditions may play an important role in regulating TIMP activity in vivo through the action of neutrophil elastase.
authors.affiliation: Department of Pathology, School of Medicine, Kanazawa University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
authors.forename: I
authors.initials: I
authors.lastname: Nakanishi
authors.forename: J
authors.initials: J
authors.lastname: Kishi
authors.forename: T
authors.initials: T
authors.lastname: Hayakawa
authors.forename: W
authors.initials: W
authors.lastname: Watorek
authors.forename: J
authors.initials: J
authors.lastname: Travis
authors.forename: H
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000201:enzymology; D002417:Cattle; D002918:Chymotrypsin / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000097:blood*; D012697:Serine Endopeptidases / Q000097:blood*; D013583:Synovial Membrane / Q000201:enzymology; D019714:Tissue Inhibitor of Metalloproteinases; D014357:Trypsin / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D012697:Serine Endopeptidases; D002918:Chymotrypsin; D010196:Pancreatic Elastase; D014357:Trypsin; D008666:Metalloendopeptidases