A Trypsin Sensitive Stromelysin Isolated from Rheumatoid Synovial Fluid is an Activator for Matrix Metalloproteinases

Abstract

Summary:The processing of synovial fluids of patients suffering from rheumatoid arthritis led to the characterization of a neutral metalloproteinase with polymorphonuclear leukocyte progelatinase and polymorphonuclear leukocyte procollagenase activating properties. The activator exhibits a relative molecular mass of M t 27000 and is an active form of Stromelysin. Thus, it reacts specifically with antibodies raised against human Stromelysin, splits polymorphonuclear leukocyte progelatinase in a manner characteristic of Stromelysin, and is inhibited by EDTA as well as by a tissue inhibitor of metalloproteinases (TIMP-2).The activator shows a high specificity for the matrix metalloproteinases, polymorphonuclear leukocyte progelatinase and polymorphonuclear leukocyte procollagenase. It shows only weak hydrolysis of casein and gelatin, and it does not activate fibroblast Μ τ 72 000 progelatinase. Brief treatment with trypsin does not lead to a significant change in the activator's relative molecular mass, but induces a rapid loss of its activating activity for polymorphonuclear leukocyte progelatinase, while its proteolytic activity against the synthetic substrate, N-(2,4)-dinitrophenyl-Pro-Gln-Gly-Ile-Ala-Gly-Gln-Z)-Arg, is increased about 3-fold. The same tryptic treatment does not affect the activator's proteolytic activity towards casein and gelatin. Introduction., . " ^ , .

Comprehensive review of Urtica dioica L. (Urticaceae) phytochemistry and anti-inflammatory properties

“…The interaction between chondrocytes and their matrix is essential for the proliferation, differentiation, and survival of cells (Kosher et al 1973;Kosher and Church 1975;Hewitt et al 1982;Shakibaei et al 1999Shakibaei et al , 2001, and a well-regulated turnover of ECM, mediated through MMPs, is required (Schulze-Tanzil et al 2001). However, an imbalance between these molecules and their natural inhibitors leads to pathological conditions (Dean et al 1989;Martel-Pelletier et al 1994), namely, OA, where high levels of MMPs lead to structural degradation (Kolkenbrock et al 1993;Manicourt et al 1995;Freemont et al 1997;Keyszer et al 1999), as a differential regulation of mRNA levels of MMPs and aggrecanases in response to IL-1b is seen in this disease (Bluteau et al 2001). The results obtained from immunofluorescence experiments and quantitative densitometry through western Blot implicate cytokine IL-1b regulation in MMP expression in human cartilage tissue when UD extract treatment is applied, which is consistent with previous studies (Horton et al 1998;Robbins et al 2000).…”