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Metalloproteinase Production (metalloproteinase + production)
Selected AbstractsLight up-regulated on B lymphocytes and monocytes in rheumatoid arthritis mediates cellular adhesion and metalloproteinase production by synoviocytesARTHRITIS & RHEUMATISM, Issue 4 2007Young Mo Kang Objective To study the expression of LIGHT (tumor necrosis factor superfamily 14) and herpesvirus entry mediator (HVEM; tumor necrosis factor receptor superfamily 14) in rheumatoid arthritis (RA) and to determine the regulatory role of LIGHT on the effector functions of fibroblast-like synoviocytes (FLS). Methods The expression of LIGHT and HVEM was assessed by immunohistochemical staining of synovial tissue and by flow cytometric analysis of mononuclear cells. The presence of HVEM and lymphotoxin , receptor was measured by reverse transcriptase,polymerase chain reaction and by flow cytometry. The regulation of effector molecules, including matrix metalloproteinases (MMPs) and adhesion molecules, was evaluated. The adhesiveness of FLS was determined by adhesion assay. Results HVEM was detected in most cell types within rheumatoid synovial tissue, while only a few cells were positive for LIGHT. In RA patients, LIGHT expression was significantly up-regulated only in CD20+ B cells and monocytes, whereas the mean fluorescence intensity of HVEM was down-regulated in mononuclear cells. The stimulation of FLS with LIGHT resulted in the production of MMPs and the expression of adhesion molecules, which were efficiently inhibited by dexamethasone. LIGHT-mediated up-regulation of MMPs and intercellular adhesion molecule 1 was blocked by inhibitors of NF-,B and JNK, whereas up-regulation of vascular cell adhesion molecule 1 was blocked by inhibitors of phosphatidylinositol 3-kinase, as well as NF-,B. Conclusion These data suggest that binding of LIGHT with its receptors may play a role in the progression of inflammation within rheumatoid synovium, especially by mediating the interactions between infiltrating inflammatory cells and stromal cells. These findings thus emphasize the relevance of LIGHT as a potential therapeutic target in RA. [source] Heterogeneous requirement of I,B kinase 2 for inflammatory cytokine and matrix metalloproteinase production in rheumatoid arthritis: Implications for therapyARTHRITIS & RHEUMATISM, Issue 7 2003Evangelos Andreakos Objective To investigate the potential role of I,B kinase 1 (IKK-1) and IKK-2 in the regulation of nuclear factor ,B (NF-,B) activation and the expression of tumor necrosis factor , (TNF,), as well as interleukin-1, (IL-1,), IL-6, IL-8, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs), in rheumatoid arthritis (RA). Methods Recombinant adenoviruses expressing ,-galactosidase, dominant-negative IKK-1 and IKK-2, or I,B, were used to infect ex vivo RA synovial membrane cultures and synovial fibroblasts obtained from patients with RA undergoing joint replacement surgery, or human dermal fibroblasts, human umbilical vein endothelial cells (HUVECs), and monocyte-derived macrophages from healthy volunteers. Then, their effect on the spontaneous or stimulus-induced release of inflammatory cytokines, VEGF, and MMPs from RA synovial membrane cells was examined. Results IKK-2 was not required for lipopolysaccharide (LPS),induced NF-,B activation or TNF,, IL-6, or IL-8 production in macrophages, but was essential for this process in response to CD40 ligand, TNF,, and IL-1. In synovial fibroblasts, dermal fibroblasts, and HUVECs, IKK-2 was also required for LPS-induced NF-,B activation and IL-6 or IL-8 production. In RA synovial membrane cells, IKK-2 inhibition had no effect on spontaneous TNF, production but significantly reduced IL-1,, IL-6, IL-8, VEGF, and MMPs 1, 2, 3, and 13. Conclusion Our study demonstrates that IKK-2 is not essential for TNF, production in RA. However, because IKK-2 regulates the expression of other inflammatory cytokines (IL-1,, IL-6, and IL-8), VEGF, and MMPs 1, 2, 3, and 13, which are involved in the inflammatory, angiogenic, and destructive processes in the RA joint, it may still be a good therapeutic target. [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] The temporal expression and localization of extracellular matrix metalloproteinase inducer (EMMPRIN) during the development of perio-dontitis in an animal modelJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2010L. Liu Liu L, Li C, Cai X, Xiang J, Cao Z, Dong W. The temporal expression and localization of extracellular matrix metalloproteinase inducer (EMMPRIN) during the development of periodontitis in an animal model. J Periodont Res 2010; 45: 541,549. © 2010 John Wiley & Sons A/S Background and Objective:, We previously demonstrated extracellular matrix metalloproteinase inducer (EMMPRIN) was associated with the matrix metalloproteinases production of human periodontitis. The aim of this study was to investigate the temporal expression and localization of EMMPRIN during ligature-induced periodontitis in rats. Material and Methods:, Periodontitis was inducd in rats by placing a thread around the cervix of the first mandibular molar. Animals were killed 3, 7, 11, 15 or 21 d after ligation. Mandibles were processed for paraffin sections and stained with hematoxylin and eosin or picrosirius red. The distance from the amelocemental junction to the alveolar crest (ACJ,AC) and the area fraction (Area%) of collagen fibers were measured. EMMPRIN was examined by immunohistochemistry and quantified by positive cell counting. Correlation analyses were then performed. Results:, Histologically, alveolar bone was gradually destroyed from day 3 to 11 and then stabilized. Collagen fibers were slightly dissociated on day 3 and extensively broken on day 7. They were reconstructed from day 11 to 21. EMMPRIN was localized predominantly in infiltrating cells and adjacent fibroblasts in interdental gingiva. The number of EMMPRIN-positive cells increased on day 3, peaked on day 7 and then gradually subsided from day 11 to 21. Statistically, there was a moderate positive correlation regarding the ACJ,AC distance (r = 0.552, p < 0.01) and a strong negative correlation with the Area% of collagen fibers (r = ,0.808, p < 0.01). In gingival epithelium, the immunoreactivity was extremely strong in basal layer cells and sulcular epithelial cells in health. It was greatly enhanced in the inflamed conditions on days 3 and 7. In the interradicular bone, EMMPRIN was localized in the osteoclasts on days 3 and 7, as well as in the osteoblasts from day 11 onwards. Conclusion:, The expression and localization of EMMPRIN are temporally varied during the development of periodontitis. In addition, the inflammation-dependent expression of EMMPRIN might be involved in alveolar bone resorption and collagen breakdown. [source] | ||||||||||