Metalloproteinase 2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas. (2004 Apr)
metalloproteinase 2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas . matrix metalloproteinases compose a family of enzymes involved in degradation of the extracellular matrix . tumor cells must penetrate the basement membrane and traverse the extracellular matrix in order to invade surrounding structures and metastasize to distant sites . gelatinases , particularly gelatinase A ( matrix metalloproteinase 2 ) , demonstrate degradative activity against components of the basement membrane and may be involved in the progression of in situ squamous cell carcinoma lesions . matrix metalloproteinase 2 overexpression has been correlated with tumor invasiveness and metastasis in a wide variety of cancer types , including squamous cell carcinoma arising on mucous membranes . however , correlation between matrix metalloproteinase 2 overexpression and the spread and prognosis of cutaneous squamous cell carcinoma has not been characterized in the literature at present . In this study , we used immunohistochemical techniques to examine the expression of matrix metalloproteinase 2 in 10 actinic keratosis , 15 in situ , 13 invasive , 13 primary ( with documented metastatic disease ) , 11 metastatic , and 8 recurrent squamous cell carcinoma cases . We found that while the average staining intensity ( scale 0 3 , 3 being strongest ) of actinic keratosis and in situ lesions was not statistically significant ( 0 . 87 1 . 3 and 0 . 75 1 . 4 , respectively ) , the average staining intensity of invasive squamous cell carcinomas ( 1 . 6 …

Matrix metalloproteinase knockout studies and the potential use of matrix metalloproteinase inhibitors in the rheumatic diseases. (2005 Aug)
matrix metalloproteinase knockout studies and the potential use of matrix metalloproteinase inhibitors in the rheumatic diseases . The matrix metalloproteinases ( MMPs ) comprise a family of enzymes that collectively can degrade all components of the extracellular matrix ( ECM ) . MMPs play an important role in many physiological processes such as embryonic development and growth , tissue remodelling and repair . overexpression and activation of MMPs contributes to many pathologies , including arthritis , cardiovascular disease , tumour progression and lung disease . targeted mutagenesis has allowed investigators to examine the contribution of MMPs to these physiological and pathologic processes . In this manuscript , we will present an up to date review of these studies . rheumatoid arthritis ( RA ) and osteoarthritis ( OA ) are chronic diseases that result in cartilage degradation and loss of joint function . MMPs have been implicated in the collagen breakdown that contributes to joint destruction . current available drugs to treat arthritis are predominantly directed towards the control of pain and / or the inflammation associated with joint synovitis but they do little to reduce joint destruction . synthetic MMP inhibitors have been developed and in animal models of OA and / or RA , these agents have shown chondroprotective effects . however , results from clinical trials in RA have been equivocal , with some studies being terminated because of lack of efficacy or safety concerns . increased understanding of the structure , regulation and function of individual …

Lung transplant ischemia reperfusion injury : metalloprotease inhibition down regulates exposure of type V collagen , growth related oncogene induced … (2008 Mar)
Lung transplant ischemia reperfusion injury : metalloprotease inhibition down regulates exposure of type V collagen , growth related oncogene induced neutrophil chemotaxis , and tumor necrosis factor alpha expression . background : immunity to type V collagen col ( V ) contributes to lung transplant rejection . matrix metalloproteases ( MMPs ) , which are induced by transplant related ischemia reperfusion injury ( IRI ) , could expose col ( V ) and regulate local IRI induced inflammation . methods : To test the hypothesis that MMPs induce col ( V ) exposure and inflammation , wistar kyoto rats were treated with the MMP inhibitor , COL 3 , before inducing lung IRI without transplantation , and in parallel studies , wistar kyoto lung donor and recipients were treated with COL 3 pre and postisograft lung transplantation . results : ischemia reperfusion injury induced growth related oncogene / CINC 1 dependent neutrophil influx , and up regulated tumor necrosis factor alpha . MMP2 and MMP9 , induced at 4 and 24 hr after IRI , respectively , were associated with detection of antigenic col ( V ) in bronchoalveolar lavage and lung interstitium because of MMP mediated matrix degradation . MMP inhibitor treatment significantly reduced polymorphonuclear leukocytes , growth related oncogene / CINC 1 , and tumor necrosis factor alpha ; abrogated MMP 9 expression ; and resulted in lower levels of antigenic col ( V ) in bronchoalveolar lavage . In the lung transplant model , inhibiting MMPs in …

Human eosinophils release matrix metalloproteinase 9 on stimulation with TNF alpha. (1999 Dec)
human eosinophils release matrix metalloproteinase 9 on stimulation with TNF alpha . background : The eosinophil is a prominent cell in allergic lung inflammation and is exposed to a range of cytokines , including TNF alpha , at the site of allergen challenge . matrix metalloproteinases ( MMPs ) and tissue inhibitors of matrix metalloproteinases ( timps ) produced by inflammatory cells are thought to play a crucial role in interstitial matrix turnover and tissue remodeling in acute and chronic lung diseases . In addition , protein kinase C is known to be important in MMP 9 expression and secretion . objective : We investigated the regulation of eosinophil derived MMP 9 and TIMP proteins by TNF alpha . methods : using RT PCR and gelatin zymography , we investigated the ability of human eosinophils to produce and secrete active MMP 9 on stimulation with TNF alpha . We also studied the production of TIMP 1 and TIMP 2 in eosinophils by using western blotting . results : The gelatinolytic activity of MMP 9 in unstimulated eosinophils was low , but it increased by 95 after TNF alpha stimulation . This increase was regulated at both the transcriptional and translational levels . The transcription inhibitor actinomycin D , the nuclear factor kappab ( nfkappab ) inhibitor N CBZ Leu Leu Leu AL , the protein synthesis inhibitor cycloheximide , and the protein kinase C inhibitor H7 significantly decreased MMP 9 activity in TNF alpha treated cells . TIMP 1 and …

Selective regulation of metalloproteinase inhibitor ( TIMP 1 ) by oncostatin M in fibroblasts in culture. (1993 Jul)
selective regulation of metalloproteinase inhibitor ( TIMP 1 ) by oncostatin M in fibroblasts in culture . tissue inhibitor of metalloproteinases ( TIMP 1 ) is a potent inhibitor of activated matrix metalloproteinases ( MMP ) such as collagenase , stromelysin , and gelatinase , and thus helps to control extracellular matrix metabolism and deposition by connective tissue cells . since various cytokines and growth factors can modify the production of MMP and TIMP 1 , we explored the action of oncostatin M ( OM ) , a unique lymphocyte and monocyte derived cytokine , on expression of these proteins . We examined the regulation of TIMP 1 expression in cultured human fibroblasts by cytokines including OM , IL 6 , leukemia inhibitory factor ( LIF ) , and IL 1 alpha . When used at levels of 5 to 50 ng / ml , OM , IL 6 , LIF , and IL 1 alpha elevated the TIMP 1 expression at the RNA level in fibroblasts of lung or synovial origin . interestingly , OM stimulation resulted in highest levels of TIMP 1 RNA and protein synthesis . however , unlike IL 1 alpha , the cytokines OM , IL 6 , and LIF did not induce MMP or PGE2 release . OM also enhanced TIMP 1 mRNA levels in the h2981 lung carcinoma and hepg2 hepatoma cell lines . The results suggest that OM as well as IL 6 and LIF , other cytokines acting through similar receptor …

Eosinophils as a source of matrix metalloproteinase 9 in asthmatic airway inflammation. (1997 Apr)
eosinophils as a source of matrix metalloproteinase 9 in asthmatic airway inflammation . bronchial asthma is characterized by eosinophil infiltration and tissue remodeling . matrix metalloproteinases ( MMPs ) are thought to play critical roles by degradating interstitial matrices in a wide range of lung diseases associated with reorganization of the airway architecture . To investigate whether MMPs are involved in the pathologic processes of bronchial asthma , we examined MMP expression in asthmatic subjects . In situ hybridization revealed abundant expression of MMP 9 ( gelatinase B ) mRNA in biopsy specimens from asthmatic subjects ( n 5 ) , with an average positive cell distribution of 117 . 8 / 41 . 1 ( mean / SEM ) / mm2 . In contrast , sparse expression of the mRNA ( 10 . 8 / 4 . 8 / mm2 ) was observed in specimens from normal subjects ( n 4 ) . The vast majority of cells expressing the mRNA were eosinophils in asthmatic tissues ( 92 . 2 / 1 . 2 ) . MMP 9 protein , which was confined to the submucosal cells in the normal subjects , was not abundantly expressed in inflammatory cells , but there was positive reactivity for MMP 9 protein in the extracellular matrix . immunoelectron microscopic analysis showed sparse immunolocalization of MMP 9 in the perinuclear spaces of eosinophils , but not in the granules . these findings suggest the overexpression of MMP 9 by eosinophils in bronchial tissues …

The role of up regulated serine proteases and matrix metalloproteinases in the pathogenesis of a murine model of colitis. (2000 Dec)
The role of up regulated serine proteases and matrix metalloproteinases in the pathogenesis of a murine model of colitis . proteinases are important at several phases of physiological and pathological inflammation , mediating cellular infiltration , cytokine activation , tissue damage , remodeling , and repair . however , little is known of their role in the pathogenesis of inflammatory bowel disease . The aim of this study was to assess the role of tissue proteases in a mouse model of colitis . proteolytic activity was analyzed , using gel and in situ zymography , in colonic tissues from severe combined immunodeficient mice with colitis induced by transfer of CD4 ( ) T lymphocytes . serine proteinase levels increased in colitic tissue , with major species of 23 kd , 30 kd , and 45 kd . Co migration and inhibition studies indicated that the 23 kd proteinase was pancreatic trypsin and that the 30 kd species was neutrophil elastase . matrix metalloproteinase ( MMP ) 9 expression , and MMP 2 and MMP 9 activation , was elevated in colitic tissues . proteinase levels followed a decreasing concentration gradient from proximal to distal colon . proteolysis was localized to infiltrating leukocytes in diseased severe combined immunodeficient mice . transmural inflammation was associated with serine proteinase and MMP activity in overlying epithelium and with marked subepithelial proteolytic activity . The results demonstrate a clear elevation in the levels and activation of proteases in colitis , potentially contributing to disease progression …

Collagenase 3 ( matrix metalloproteinase 13 ) expression is induced in oral mucosal epithelium during chronic inflammation. (1998 Jul)
collagenase 3 ( matrix metalloproteinase 13 ) expression is induced in oral mucosal epithelium during chronic inflammation . increased proliferation of mucosal epithelium during inflammation is associated with degradation of subepithelial connective tissue matrix and local invasion of the epithelial cells . Here we have studied , whether collagenase 3 ( MMP 13 ) , a collagenolytic matrix metalloproteinase with an exceptionally wide substrate specificity , is expressed in the epithelium of chronically inflamed mucosa . examination of human gingival tissue sections from subjects with chronic adult periodontitis with in situ hybridization revealed marked expression of MMP 13 in basal cells of some epithelial rete ridges expanding into connective tissue . immunohistochemical staining demonstrated that these cells also expressed strongly laminin 5 , suggesting that they are actively migrating cells . A strong signal for MMP 13 mRNA was occasionally also noted in the suprabasal epithelial cells facing the gingival pocket , whereas no collagenase 1 ( MMP 1 ) mRNA was detected in any areas of the epithelium . MMP 13 expression was also detected in fibroblast like cells associated with collagen fibers of the inflamed subepithelial connective tissue . In organ culture of human oral mucosa , MMP 13 mRNA expression was observed in epithelial cells growing into connective tissue of the specimens . regulation of MMP 13 expression was examined in cultured normal nonkeratinizing epithelial cells isolated from porcine periodontal ligament . In these cells , MMP 13 expression at the mRNA and protein level was potently …

Proteolytic activation of corneal matrix metalloproteinase by pseudomonas aeruginosa elastase. (1993 Feb)
proteolytic activation of corneal matrix metalloproteinase by pseudomonas aeruginosa elastase . purified pseudomonas aeruginosa elastase cleaved a 65 kDa gelatinase inactive proenzyme form of matrix metalloproteinase ( MMP 2 ) from human corneal fibroblasts into a biologically active fragment with an approximate molecular mass of 58 kDa . however , purified pseudomonal alkaline protease did not cleave MMP 2 appreciably . since activated MMP 2 is known to degrade native type IV , V and VII collagens , all components of the corneal basement membrane or stroma , our results suggest a new role for pseudomonal elastase in the pathogenesis of corneal infection , inflammation and ulceration .

Enhanced production of tissue inhibitor of metalloproteinases by peripheral blood mononuclear cells of rheumatoid arthritis patients responding to methotrexate treatment. (2000 Sep)
enhanced production of tissue inhibitor of metalloproteinases by peripheral blood mononuclear cells of rheumatoid arthritis patients responding to methotrexate treatment . objective : To determine the effects of methotrexate ( MTX ) treatment of rheumatoid arthritis ( RA ) patients ( a ) on the circulating levels and ( b ) on the ex vivo production of matrix metalloproteinase 1 ( MMP 1 ) and tissue inhibitor of metalloproteinases 1 ( TIMP 1 ) by peripheral blood mononuclear cells ( pbmnc ) . methods : circulating levels , spontaneous ex vivo and in vitro production of MMP 1 , TIMP 1 and interleukin 6 ( IL 6 ) were assessed by immunoassays in sera and culture supernatants of pbmnc derived from 27 patients with active RA before and 3 months after beginning MTX treatment and from seven healthy subjects . The production and serum levels of MMP 1 , TIMP 1 and IL 6 were correlated to the clinical response . results : pbmnc of RA patients showing / 20 improvement of the paulus index after 3 months of MTX treatment ( responders ; n 16 ) exhibited a significantly enhanced production of spontaneous TIMP 1 ex vivo which was associated with the enhanced synthesis of IL 6 . In contrast , pbmnc of 11 patients with 20 improvement and / or progression of disease showed a marked reduction of TIMP 1 and IL 6 secretion . circulating levels of TIMP 1 remained unchanged in both groups whereas serum IL …

Inflammation responsive transcription factors SAF 1 and c Jun / c Fos promote canine MMP 1 gene expression. (2006 Feb)
inflammation responsive transcription factors SAF 1 and c Jun / c Fos promote canine MMP 1 gene expression . matrix metalloproteinase 1 ( MMP 1 ) has been implicated in the pathogenesis of osteoarthritis ( OA ) due to its ability to degrade extracellular matrix component of the joint cartilage tissue that cushions the bone from frictional damage . canine hip dysplasia , a developmental orthopedic disease which results in arthritic condition as is seen in human OA is an excellent system to study the involvement of MMP 1 in the pathogenesis of OA . To date , however , no report is available regarding canine MMP 1 promoter and the regulatory mechanism by which increased synthesis of MMP 1 protein might be regulated . To gain an insight , we have investigated the promoter region of canine MMP 1 . MMP 1 synthesis in the resident cells of arthritic joints is regulated via two major cytokines , IL 1beta and TNF alpha . By using a series of progressively deleted reporter constructs , multiple cytokine responsive elements were identified in the proximal promoter region of canine MMP 1 . these include DNA binding elements of AP 1 and SAF 1 transcription factors . mutation of AP 1 or SAF 1 element resulted in marked reduction in the cytokine responsiveness of MMP 1 promoter . We show that AP 1 and SAF 1 DNA binding activities are increased in cytokine stimulated cells as well as in osteoarthritic cartilage tissues . …

Differential temporal expression of matrix metalloproteinases after spinal cord injury : relationship to revascularization and wound healing. (2003 Sep)
differential temporal expression of matrix metalloproteinases after spinal cord injury : relationship to revascularization and wound healing . object : matrix metalloproteinases ( MMPs ) , particularly MMP 9 / gelatinase B , promote early inflammation and barrier disruption after spinal cord injury ( SCI ) . early blockade of MMPs after injury provides neuroprotection and improves motor outcome . there is recent evidence , however , that MMP 9 and MMP 2 / gelatinase A participate in later wound healing in the injured cord . The authors therefore examined the activity of these gelatinases during revascularization and glial scar formation in the contused murine spinal cord . methods : gelatinase activity was evaluated using gelatin zymography 24 hours after a mild , moderate , or severe contusion injury . The active form of MMP 2 was not detected , whereas MMP 9 activity was evident in all SCI groups and rose with increasing injury severity . The temporal expression of gelatinases was then examined using gelatin zymography after a moderate SCI . The active form of MMP 9 was most prominent at 1 day , extended through the early period of revascularization , and returned to control by 14 days . The active form of MMP 2 appeared at 7 days postinjury and remained elevated compared with that documented in sham treated mice for at least 21 days . increased MMP 2 activity coincided with both revascularization and glial scar formation . using in situ zymography , gelatinolytic activity …

Molecular signatures of vascular injury are associated with early growth of intracerebral hemorrhage. (2004 Dec)
molecular signatures of vascular injury are associated with early growth of intracerebral hemorrhage . background AND purpose : To investigate whether molecular markers of inflammation and endothelial injury are associated with early growth of intracerebral hemorrhage ( ICH ) . methods : In a multicenter prospective study , we determined concentrations of interleukin 6 ( IL 6 ) , tumor necrosis factor alpha ( TNF alpha ) , matrix metalloproteinase 9 ( MMP 9 ) , and cellular fibronectin ( c Fn ) in blood samples obtained on admission from 183 patients with primary hemispheric ICH of 12 hours duration . patients had a neurological evaluation and a computed tomography ( CT ) scan performed at baseline and at 48 / 6 hours . early growth of the ICH was defined as a volume increase 33 between the 2 CT examinations for ICH with a baseline volume 20 mL and 10 for ICH or 20 mL . clinical , radiological , and biochemical predictive factors of ICH enlargement were analyzed by logistic regression analysis . results : fifty four ( 29 . 5 ) patients showed a relevant early growth of ICH . High leukocyte count and fibrinogen levels , low platelet count , and intraventricular bleeding were associated with early ICH growth in bivariate analyses . plasma concentrations of IL 6 ( median quartiles : 19 . 6 13 . 6 ; 29 . 9 versus 15 . 9 11 . 5 ; 19 . 8 pg / mL …

Increased alveolar and plasma gelatinases activity during postpump syndrome : inhibition by inhaled nitric oxide. (2006 Oct)
increased alveolar and plasma gelatinases activity during postpump syndrome : inhibition by inhaled nitric oxide . postpump syndrome is associated with systemic inflammation . matrix metalloproteinases ( MMP ) 2 and 9 contribute to proinflammatory and platelet activator reactions . nitric oxide ( NO ) is involved in the regulation of MMPs . The objectives of our study were to investigate the intensity of inflammation induced by 3 different surgical procedures , the effects of inflammation on the activity of MMPs , and the regulation of inflammation by inhaled NO ( 20 ppm ) . inhaled NO was initiated immediately after tracheal intubation and maintained for the total duration of the experiments . thirty pigs were equally randomized into 6 groups sham ; sham NO ; cardiopulmonary bypass ; bypass NO ; bypass lipopolysaccharide ( 1 microg / kg for 50 min ) ; bypass lipopolysaccharide NO and animals were subjected to anesthesia and mechanical ventilation up to 24 h . The levels of MMP 2 and MMP 9 in plasma and bronchoalveolar lavage were measured using zymography . bypass resulted in a time dependent rise in MMP activity , an effect potentiated by lipopolysaccharide . inhaled NO attenuated the effects of bypass lipopolysaccharide . these results confirm that MMP 2 and MMP 9 are associated with the inflammatory process causing the postpump syndrome . preemptive and continuous administration of inhaled NO helps to prevent increased MMP 2 and MMP 9 activity .

Protease activated receptor 2 activating peptide sligrl inhibits bacterial lipopolysaccharide induced recruitment of polymorphonuclear leukocytes into the airways of mice. (2002 May)
protease activated receptor 2 activating peptide sligrl inhibits bacterial lipopolysaccharide induced recruitment of polymorphonuclear leukocytes into the airways of mice . protease activated receptor 2 ( PAR2 ) acts as a receptor for trypsin and trypsin like enzymes . The role of this receptor in airway inflammation is uncertain . In this study we assessed the effect of activation of PAR2 following intranasal administration of the peptide activator of PAR2 , sligrl , over 72 h in mice . The extent of immune cell infiltration into the airways and activities of matrix metalloprotease 2 ( MMP 2 ) and MMP 9 were assessed in bronchoalveolar lavage ( BAL ) by differential cell counts and gelatin zymography , respectively . sligrl did not cause a change in the number or types of cells retrieved in BAL at any time point and did not alter the levels of MMP 2 and MMP 9 present in BAL . In contrast , similar intranasal administration of bacterial lipopolysaccharide ( LPS ) caused a large influx of neutrophilic polymorphonuclear leukocytes , which was associated with increased MMP 2 at 3 h only and MMP 9 activity from 3 72 h . simultaneous administration of sligrl and LPS transiently potentiated increased MMP 9 activity at 3 h but markedly inhibited neutrophil influx and elevated MMP 2 activity at 3 h . these findings suggest that PAR2 agonists may be useful therapeutic molecules in pulmonary inflammatory diseases .

An orally active matrix metalloproteinase inhibitor , ONO 4817 , reduces dextran sulfate sodium induced colitis in mice. (2004 Nov)
An orally active matrix metalloproteinase inhibitor , ONO 4817 , reduces dextran sulfate sodium induced colitis in mice . objective : Over expression of matrix metalloproteinases ( MMPs ) can accelerate tissue destruction and disrupt subsequent tissue repair . A dextran sulfate sodium ( DSS ) colitis model was established to examine the effects of MMP inhibition , by an orally active MMP inhibitor ONO 4847 , on colonic inflammation . materials AND methods : acute colitis was induced in female BALB / c mice by giving 8 DSS orally in drinking water for 7 days . The animals were randomized into groups receiving different concentrations of ONO 4847 or vehicle by oral gavage every day . mRNA levels of 4 MMPs and a tissue inhibitor of MMP ( TIMP 1 ) were measured by RT PCR in intestinal tissue isolated from mice after DSS administration . colonic mucosal injury and inflammation were evaluated clinically , biochemically , and histologically . The clinical disease activity index ( DAI ) , including body weight loss , stool consistency , and blood in feces , was examined . moreover , mucosal tumor necrosis factor ( TNF ) alpha and interferon ( IFN ) gamma were determined by immunoassay . results : The intestinal expression of MMP 3 , 7 , 9 , and 12 and TIMP 1 mRNA was upregulated after DSS administration . shortening of the colon was significantly reversed by ONO 4847 at a dose of 30 mg / kg …

Effects of irradiation on endothelial cell polymorphonuclear leukocyte interactions. (1986 Aug)
effects of irradiation on endothelial cell polymorphonuclear leukocyte interactions . prominent early effects of irradiation include neutrophilic vasculitis and interstitial inflammation . To examine the role of the endothelium in these events , bovine aortic endothelial cells ( EC ) were irradiated ( 5 Gy ) under ambient conditions followed by measurements of neutrophil chemotaxis toward conditioned media and adherence to EC . neutrophil chemotactic activity increased at 4 , 24 , and 72 h in both the sham treated ( 4 . 2 / 2 . 5 , 15 . 2 / 4 . 8 , and 20 . 0 / 2 . 7 microns , respectively ) and irradiated EC conditioned media ( 5 . 0 / 2 . 1 , 18 . 7 / 4 . 5 , and 24 . 1 / 3 . 4 microns , respectively ) , and the difference between them was significant at 72 h . The chemoattractant was trypsin sensitive , heat resistant , and chemotactic . It was not present in the EC sonicate . adherence of neutrophils to EC that were irradiated 4 h earlier ( 19 . 3 / 4 . 2 ) increased compared with controls ( 11 . 1 / 2 . 4 ) and was similar to EC pretreated with zymosan activated serum ( 22 . 0 / 4 . 0 ) , which is a potent inducer of adherence . Thus , following irradiation , bovine aortic EC have greater neutrophil chemotactic activity …

Clinical significance of gelatinases in septic arthritis of native and replaced knees. (2004 Nov)
clinical significance of gelatinases in septic arthritis of native and replaced knees . We hypothesized that more gelatinases appear in effusions of septic arthritis than aseptic arthritis . This study examined the laboratory variables of inflammation and the levels of gelatinase A and B ( matrix metalloproteinases 2 and 9 ) in 75 effusions from the knees of 37 patients with inflammatory arthritis and compared them with effusions of septic and aseptic arthritis . gelatin zymography revealed that the levels of the latent matrix metalloproteinase 9 were higher in 24 effusions of septic arthritis than in 51 effusions of aseptic arthritis . The latent matrix metalloproteinase 9 levels of septic arthritis also correlated with the neutrophil counts in effusions . significantly more activated matrix metalloproteinases 2 and 9 appeared in effusions of septic arthritis in native and replaced knees than in effusions of aseptic arthritis . A high matrix metalloproteinase 9 level and the appearance of activated matrix metalloproteinases 2 and 9 may distinguish septic from aseptic arthritis , even in cases with a low neutrophil count in the replaced knee . joint aspiration may not only reduce the bacteria counts , endotoxins , and proinflammatory cytokines , but also decrease the amount of matrix metalloproteinases in effusions that attack the extracellular matrix of native and artificial joints .

Effect of high dose inhaled steroid on cells , cytokines , and proteases in induced sputum in chronic obstructive pulmonary … (1999 Dec)
effect of high dose inhaled steroid on cells , cytokines , and proteases in induced sputum in chronic obstructive pulmonary disease . inhaled corticosteroids are widely prescribed for the treatment of stable chronic obstructive pulmonary disease ( COPD ) , despite lack of proven efficacy . because COPD involves airway inflammation and probable protease antiprotease imbalance , we examined the effect of high dose fluticasone propionate on markers of activity of both pathogenetic mechanisms . thirteen patients with COPD were treated with fluticasone propionate ( 500 microg twice a day ) for 4 wk , delivered via MDI and spacer , in a double blind crossover study . there was no clinical benefit in terms of lung function or symptom scores , and induced sputum inflammatory cells , percentage neutrophils , and IL 8 levels were unchanged . sputum supernatant elastase activity , matrix metalloproteinase ( MMP ) 1 , MMP 9 , and the antiproteases secretory leukoprotease inhibitor ( SLPI ) and tissue inhibitor of metalloproteinase ( TIMP ) 1 were similarly unaffected by treatment . these results add to previous evidence that inhaled steroids have no anti inflammatory action in stable COPD . furthermore , inhaled steroids do not appear to redress the protease antiprotease imbalance that is thought to be important in the pathogenesis of airway obstruction .

Modulation of matrix metalloproteinase production from human lung fibroblasts by type 4 phosphodiesterase inhibitors. (2004 Jun)
modulation of matrix metalloproteinase production from human lung fibroblasts by type 4 phosphodiesterase inhibitors . Over expression of matrix metalloproteinases by lung fibroblasts has been blamed for much of the tissue destruction associated with airway inflammation . because cyclic AMP is known to regulate fibroblast proliferation , as well as cytokine and extracellular matrix protein production , the current study was designed to evaluate the ability of three selective phosphodiesterase ( PDE ) type 4 inhibitors , rolipram , cilomilast and CI 1044 , to inhibit extracellular matrix degradation . using zymography and elisa , we found that pro MMP 2 release was enhanced following 24 h treatment of human lung fibroblast ( MRC 5 ) with TGF beta1 ( 10 ng / ml ) or TNF alpha ( 10 ng / ml ) , whereas PMA ( 0 . 02 microm ) had no effect . One hour of pre incubation with PDE4 inhibitors ( 10 microm ) induced an inhibition of TNF alpha stimulated pro MMP 2 release . zymography and immunoblotting revealed that fibroblasts cultured with PMA or TNF alpha released increased amounts of pro MMP 1 , whereas TGF beta1 had no effect . incubation with CI 1044 or cilomilast significantly prevented the TNF alpha increase in pro MMP 1 . these results suggest that PDE4 inhibitors are effective in inhibiting the pro MMP 2 and pro MMP 1 secretion induced by TNF alpha and might underline a potential therapeutic benefit of selective PDE4 inhibitors in …