Detail of "152787-66-1"

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A major role for matrix metalloproteinases in T cell injury in the gut

A major role for matrix metalloproteinases in T cell injury in the gut. Pender, Sylvia L. F.; Tickle, Simon P.; Docherty, Andrew J. P.; Howie, Duncan; Wathen, Neville C.; MacDonald, Thomas T. (Dep. Pediatric Gastroenterology, St. Bartholomew's, London, UK). Journal of Immunology, 158(4), 1582-1590 (English) 1997 American Association of Immunologists. CODEN: JOIMA3. ISSN: 0022-1767. DOCUMENT TYPE: Journal CA Section: 15 (Immunochemistry) Section cross-reference(s): 14, 17 Activated lamina propria T cells responding to luminal Ags are thought to be important in celiac disease and Crohn's disease, and T cells responding to foreign MHC products are also important in intestinal graft-vs.-host disease and intestinal transplant rejection. However, the mechanism(s) by which T cells mediate damage in the gut is not known. The authors have previously shown that activation of lamina propria T cells by PWM in explant cultures of second trimester human small intestine produces severe tissue injury, with epithelial cell shedding and loss of villi. In this study, the authors have investigated the role of matrix metalloproteinases in this system. Organ culture supernatants of explants stimulated with PWM showed a 3-fold increase in the concn. of interstitial collagenase and a 10-fold increase in stromelysin-1 compared with control explant culture supernatants. Tissue inhibitors of metalloproteinase-1 and -2 concns. were unchanged. Increased metalloproteinase enzymic activity was detected by gelatin and casein zymog. Western blotting revealed the active forms of interstitial collagenase and stromelysin-1 in PWM-stimulated culture supernatants. 157549-54-7 and 152787-66-1 which are cas registry numbers of chemicals are mentioned. Up-regulation of mRNA for interstitial collagenase, stromelysin-1, and gelatinase-B was also seen. Nanomolar amts. of recombinant stromelysin-1 added directly to explants produced rapid severe tissue injury. PWM-induced mucosal injury was inhibited by a synthetic peptidomimetic inhibitor of matrix metalloproteinases. Mesenchymal cells isolated from the mucosa of human fetal small intestine produced increased amts. of interstitial collagenase, gelatinase A, and stromelysin-1 when stimulated with IL-1b or TNF-a. These results suggest that T cell activation in the lamina propria results in increased prodn. of matrix metalloproteinases, which by degrading the lamina propria matrix represent a major pathway by which T cells cause injury in the gut. .

In vivo activation of gelatinase B/MMP-9 by trypsin in acute pancreatitis is a permissive factor in streptozotocin-induced diabetes

In vivo activation of gelatinase B/MMP-9 by trypsin in acute pancreatitis is a permissive factor in streptozotocin-induced diabetes. Descamps, Francis J.; Martens, Erik; Ballaux, Florence; Geboes, Karel; Opdenakker, Ghislain (Rega Institute for Medical Research, Laboratory of Molecular Immunology, University of Leuven, Louvain, Belg.). Journal of Pathology, 204(5), 555-561 (English) 2004 John Wiley & Sons Ltd. CODEN: JPTLAS. ISSN: 0022-3417. DOCUMENT TYPE: Journal CA Section: 14 (Mammalian Pathological Biochemistry) Matrix metalloproteinases, in particular gelatinase B/MMP-9, are key mediators in autoimmune diseases like multiple sclerosis and rheumatoid arthritis, but their pathogenic roles in diabetes are not well established. Gelatinase B has previously been shown to be upregulated in pancreas tissue from patients with acute and chronic pancreatitis and was suggested to exacerbate diabetes by cleaving insulin. In this study, the role of gelatinase B in diabetes was investigated using 2 streptozotocin-induced animal models of type I diabetes. In both a hyperacute and a subacute model, gelatinase B upregulation was found to be assocd. with disease activity. However, gelatinase B deficiency did not significantly protect against diabetes development, and wild-type and gelatinase B-deficient animals behaved similarly in terms of b-cell apoptosis or necrosis. The fact that gelatinase B was found almost exclusively as the inactive pro-enzyme in most of the streptozotocin-induced diabetic animals may explain the lack of a gelatinase B effect. On the contrary, gelatinase B was completely activated in a minority (15%) of wild-type animals. This coincided with exocrine pancreatic inflammation, as revealed by the presence of active trypsin. The discovery of in vivo activation of progelatinase B by trypsin in acute pancreatitis is extended in a model of caerulein-induced pancreatitis. In the latter model, trypsinogen activation is systematically achieved and gelatinase B is found in its active form. In conclusion, gelatinase B itself is not a causative factor but, when activated by endogenous trypsin, is a permissive factor for insulin degrdn. and diabetes.Except for chemicals metioned above, 50-99-7 and 152787-66-1 are also used. .