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MMP Production (mmp + production)
Selected AbstractsActivated ,2 macroglobulin induces matrix metalloproteinase 9 expression by low-density lipoprotein receptor-related protein 1 through MAPK-ERK1/2 and NF-,B activation in macrophage-derived cell linesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010Leandro C. Cáceres Abstract Macrophages under certain stimuli induce matrix metalloproteinase 9 (MMP-9) expression and protein secretion through the activation of MAPK-ERK and NF-,B signaling pathways. Previously, we demonstrated that activated ,2 -macroglulin (,2M*) through the interaction with its receptor low-density lipoprotein receptor-related protein 1 (LRP1) induces macrophage proliferation mediated by the activation of MAPK-ERK1/2. In the present work, we examined whether ,2M*/LRP1interaction could induce the MMP-9 production in J774 and Raw264.7 macrophage-derived cell lines. It was shown that ,2M* promoted MMP-9 expression and protein secretion by LRP1 in both macrophage-derived cell lines, which was mediated by the activation of MAPK-ERK1/2 and NF-,B. Both intracellular signaling pathways activated by ,2M* were effectively blocked by calphostin-C, suggesting involvement of PKC. In addition, we demonstrate that ,2M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA-AM, the ,2M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1, and NF-,B, it was shown that the ,2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the ,2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression. J. Cell. Biochem. 111: 607,617, 2010. © 2010 Wiley-Liss, Inc. [source] Chemically modified tetracyclines stimulate matrix metalloproteinase-2 production by periodontal ligament cellsJOURNAL OF PERIODONTAL RESEARCH, Issue 5 2006M. M. Bildt Background and Objective:, The purpose of this study was to investigate the effects of chemically modified tetracyclines (CMTs) on the production of gelatinases [matrix metalloproteinase (MMP)-2 and -9] by human periodontal ligament (PDL) cells, and on the activity of recombinant gelatinases. Material and Methods:, Human PDL cells were cultured with CMT-1, -3, -5, -7 or -8 in concentrations of 0, 1, 5, 10, 20, 50, 100, 200 and 500 µm. Gelatin zymography was used to determine MMP-2 and -9 production of the cells. The amount of DNA present in the cultures was analyzed using a fluorescent assay. The cytotoxicity of the CMTs was also determined. Recombinant human MMP-2 and -9 were incubated with the CMTs (0,500 µm) and their activity was analyzed using an internally quenched fluorogenic substrate. Results:, MMP-2 production was stimulated up to sevenfold by CMT-1, -3, -7 and -8 at low concentrations (10,200 µm). No significant amounts of MMP-9 were produced. In contrast, MMP-2 and -9 activity was reduced by ,,10,40-fold at higher concentrations (200,500 µm). CMT-5 had no effect on the production or on the activity of MMP-2 and -9. Only CMT-3 and -8 had cytotoxic effects on the PDL cells at the highest concentrations. Conclusion:, Surprisingly, CMTs are able to stimulate MMP-2 production at relatively low concentrations. However, at higher concentrations they exert a much stronger inhibitory effect on gelatinase activity. A possible stimulatory effect of CMTs on MMP production should be considered in their clinical use. [source] Stimulation of epithelial cell matrix metalloproteinase (MMP-2, -9, -13) and interleukin-8 secretion by fusobacteriaMOLECULAR ORAL MICROBIOLOGY, Issue 5 2008U. K. Gursoy Background/aims:, Bacterial pathogens involved in periodontal diseases exert their destructive effects primarily by stimulating the host cells to increase their secretion of proinflammatory cytokines and matrix metalloproteinases (MMPs). This study aimed to determine the epithelial cell matrix metalloproteinase and interleukin-8 (IL-8) secretion upon exposure to fusobacteria. Methods:, Eight different oral and non-oral Fusobacterium strains were incubated with HaCaT epithelial cells. Gelatin zymography and Western blot analysis were performed to detect collagenase 3 (MMP-13), gelatinase A (MMP-2), gelatinase B (MMP-9), and IL-8 secretion by epithelial cells. Results:, All Fusobacterium strains, especially Fusobacterium necrophorum ATCC 25286, Fusobacterium nucleatum ATCC 25586, and Fusobacterium varium ATCC 51644, increased MMP-9 and MMP-13 secretion. Fusobacterium simiae ATCC 33568, and to a lesser extent F. nucleatum and F. necrophorum, increased epithelial MMP-2 secretion. F. nucleatum and F. necrophorum also increased IL-8 secretion. F. varium ATCC 27725, a strain that only weakly stimulated MMP production, strongly increased the IL-8 production, suggesting that their expression is differently regulated. Conclusion:, We conclude that the pathogenic potential of fusobacteria may partly result from their ability to stimulate secretion of MMP-9, MMP-13, and IL-8 from epithelial cells. [source] DOES MATRIX METALLOPROTEINASE ACTIVITY PREDICT SEVERITY OF ACUTE PANCREATITIS?ANZ JOURNAL OF SURGERY, Issue 9 2006Murat Aynaci Background: Matrix metalloproteinases (MMP) modulate end-organ complications of acute pancreatitis, but the correlation between increased MMP production and histological severity of disease remains unclear. We examined the role of MMP and pancreas histology on experimental acute pancreatitis. Methods: Forty male Wistar albino rats were subjected to cerulein-induced pancreatitis (8, 16, 24 and 32 h groups) or sham treatment. The animals were killed at different time points and pancreatic tissues were harvested to assess MMP (1, 2 and 9) activity and inflammatory changes. Results: Compared with other groups, 8 h group had decreased tissue MMP-1 concentrations. MMP-9 concentrations were lower in 24-h and 32-h groups, as were histological severity scores. MMP-2 activity did not differ among groups. Pancreatitis was prominent in 8-h, 16-h and 24-h groups by means of histology. Conclusion: Induction of pancreatitis by cerulein altered pancreatic MMP levels in the early phase of inflammation. Inhibition of MMP-2 and MMP-9 paralleled histological scores. Therefore, MMP may have a predictive value to assess histological severity. [source] The invasive behaviour of prostatic cancer cells is suppressed by inhibitors of tyrosine kinase,APMIS, Issue 1 2006HAAKON SKOGSETH Proteolytic enzymes, and especially urokinase plasminogen activator (uPA), play an important role in tumour invasion and metastasis. Previously we demonstrated that the production of urokinase plasminogen activator (uPA) was decreased by several tyrosine kinase inhibitors (TKI) in two prostatic carcinoma cell lines. The effect of the two TKI genistein and tyrphostin AG-1478 was investigated in the prostate carcinoma cell lines PC-3 and DU-145. A reconstituted basal lamina (Matrigel) was used as a migration barrier. The production of matrix metalloproteinases (MMP) was also measured. Roles of plasminogen and uPA were examined. Cell invasion was increased by plasminogen, but this enhanced cell migration was counteracted by TKI treatment. The increased cell invasion induced by plasminogen was decreased by at least 60% in both cell lines when ,-2 anti-plasmin was added to the assay. Cells in the absence of plasminogen were not affected by TKI. External uPA failed to regenerate the decreased cell invasion caused by TKI. The production of MMP was inhibited by both TKI. Our results indicate a possible role of TKI as inhibitors of cancer cell invasion by inhibiting uPA and MMP production. [source] Crucial role of macrophages in matrix metalloproteinase,mediated cartilage destruction during experimental osteoarthritis : Involvement of matrix metalloproteinase 3ARTHRITIS & RHEUMATISM, Issue 1 2007Arjen B. Blom Objective To explore the involvement of synovial macrophages in early cartilage damage in osteoarthritis (OA), and to identify the role of matrix metalloproteinase 3 (MMP-3) in the pathology of early and late OA. Methods The role of synovial macrophages in MMP-mediated damage in OA was studied by depleting synovial macrophages prior to elicitation of a collagenase-induced instability model of OA. The expression of MMP in synovium and cartilage was monitored using TaqMan analysis. In spontaneous and induced OA, cartilage pathology was scored in MMP-3,knockout mice and control mice, by histologic assessment and VDIPEN staining. Results On day 14 following induction of OA, MMP-mediated neoepitopes were detected in cartilage from mice with mild experimental OA (mean ± SD positively stained surface area 20 ± 3.2%). Remarkably, by depleting synovial macrophages prior to induction of OA, the generation of MMP-induced neoepitopes was largely prevented (mean ± SD positively stained surface area 5 ± 1%; P< 0.001), indicating an important role for synovial macrophages in the occurrence of MMP-mediated cartilage damage. We observed a strong decrease in MMP-3 and MMP-9 expression in synovial but not cartilage tissue in macrophage-depleted joints. Among 2-year-old mice, spontaneous OA,like changes in the lining layer were significantly decreased in MMP-3,knockout mice compared with control mice. Even more striking was the 67% reduction in the occurrence of severe cartilage damage in MMP-3,knockout mice. In addition, MMP-mediated VDIPEN expression was significantly decreased, indicating reduced MMP-mediated cartilage breakdown. Conclusion The results of this study prove that MMP-3 is involved in the generation of severe cartilage damage in murine OA. Synovial macrophages are crucial in early MMP activity and appear to mediate MMP production in synovium rather than cartilage. [source] Suppressive activity of fexofenadine hydrochloride on metalloproteinase production from nasal fibroblasts in vitroCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2004K. Asano Summary Background Allergic rhinitis (AR) is an inflammatory disease characterized by nasal wall remodelling with intense infiltration of eosinophils and mast cells/basophils. Matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are the major proteolytic enzymes that induce airway remodelling. These enzymes are also important in the migration of inflammatory cells through basement membrane components. Objective We evaluated whether fexofenadine hydrochloride (FEX), the carboxylic acid metabolite of terfenadine with selective H1 -receptor antagonist activity, could inhibit MMP production from nasal fibroblasts (NFs) in response to TNF-, stimulation in vitro. Methods NFs were established from nasal polyp-derived fibroblasts (PFs) taken from patients with AR. Nasal mucosal fibroblasts (MFs) were also induced from nasal mucosal tissues from septal deformity patients without allergy. PF and MF (2 × 105 cells/mL, each) were stimulated with TNF-, in the presence of various concentrations of FEX. After 24 h, culture supernatants were obtained and assayed for MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 levels by ELISA. The influence of FEX on mRNA expression of MMPs and TIMPs in 4 h-cultured cells was also evaluated by real-time RT-PCR. Furthermore, nuclear factor-,B (NF-,B) activation in fibroblasts treated with FEX for 4 h was examined by ELISA. Results FEX at more than 350 ng/mL inhibited the production of MMP-2 and MMP-9 from both PF and MF in response to TNF-, stimulation, whereas TIMP-1 and TIMP-2 production was scarcely affected by FEX. FEX also inhibited MMP mRNA expression and NF-,B activation in PF and MF after TNF-, stimulation. Conclusion The present data suggest that the attenuating effect of FEX on MMP-2 and -9 production from NFs induced by inflammatory stimulation may underlie the therapeutic mode of action of the agent on allergic diseases, including AR. [source] | ||||||||||