Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the increased production of autoantibodies and by systemic clinical manifestations and damage to multiple organs. The aim of the present study was to analyse matrix metalloproteinase (MMP)-9 activity in sera of patients with active and inactive SLE in order to evaluate its role in the pathogenesis and course of the disease, as well as its diagnostic value. We measured activity levels of MMP-9 and MMP-2, using both gel zymography and activity assay kits, in sera of 40 SLE patients and of 25 healthy controls. We found that MMP-9 activity, but not MMP-2 activity, is significantly elevated in the sera of SLE patients compared with sera samples of healthy controls. High activity levels of MMP-9 were determined in sera of 68% of the SLE patients. Elevated levels of MMP-9 were correlated with the presence of discoid rash, Raynaud phenomenon, pneumonitis, mucosal ulcers and anti-phospholipid antibodies. Changes in activity levels of MMP-9, but not of MMP-2, were observed in sera of the same patient at different periods of the disease course. High levels of MMP-9 did not correlate with disease activity index (SLEDAI, BILAG) in female patients, but correlated with SLE activity in the group of male patients. The results of the present study suggest that MMP-9 plays a role in the pathogenesis of SLE.
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PMID:Activity of matrix metalloproteinase-9 is elevated in sera of patients with systemic lupus erythematosus. 1187 67

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the increased production of autoantibodies and by T cell dysfunction associated with general clinical manifestations. A model of induced experimental SLE by the immunization with the human monoclonal anti-DNA 16/6Id(+) autoantibody and a model of the SLE-prone mice (NZB x NZW)F1 were used in the present study. Two peptides based on the complementarity determining regions (CDR) 1 and 3 of a murine monoclonal anti-DNA 16/6Id(+) autoantibody were shown to ameliorate spontaneous and induced SLE in mice. We demonstrate here that levels of matrix metalloproteinase (MMP)-3 and MMP-9 were elevated in plasma and kidneys of SLE-afflicted mice. Levels of both MMP-3 and MMP-9 were elevated in kidneys of mice with the 16/6Id induced experimental SLE already in the early phases of disease development. However, increased levels of only MMP-3 were detected in the plasma at the early stages of disease, while MMP-9 activity was elevated later, when clinical manifestations were already observed. Treatment of SLE-afflicted mice, with the CDR1-based peptide that ameliorates disease manifestations in mice, led to a reduction in MMP-9 activity and in MMP-3 protein levels both in plasma and in kidneys. We thus suggest that these enzymes may play a pathogenic role in the disease and may serve as markers for the determination of disease progression or amelioration.
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PMID:A peptide based on an anti-DNA autoantibody downregulates matrix metalloproteinases in murine models of lupus. 1248 97

During the course of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), several immune and neuroendocrine changes associated with pregnancy may exert positive (amelioration) or negative (exacerbation) effects on the clinical outcome. In order to shed light on the mechanisms underlying these responses, we performed a prospective longitudinal study in RA and SLE pregnant women, including healthy pregnant women as a control group. Cytokine messenger RNA (mRNA) expression assessed by quantitative competitive polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMC), cytokine levels and lymphocyte proliferation responses (LPR) following phytohaemagglutinin (PHA) stimulation of PBMC, plasma metalloprotease-9 activity (MMP-9) and hormonal status during pregnancy were determined. TNFa was the most abundant cytokine mRNA expressed in PBMC in all groups studied (healthy pregnant women, RA and SLE pregnant patients). However, a general TH2 response reflected by high IL-10 levels was found in RA, as well as SLE, patients. A significant change in IFN-gamma was observed in RA patients but only during the first trimester of pregnancy. This compared with a major TH1 response in healthy pregnant women. Interestingly, our study showed a homogeneous hormonal pattern in RA and SLE patients. Although decreased cortisol levels were observed in all patients studied, this is possibly related to the remission of disease activity status brought about by steroid treatment before and during pregnancy. In summary, we suggest that complex immune and hormonal networks are involved in pregnancy and that rheumatic diseases are very dynamic immune processes that cannot be described with a clear-cut cytokine profile. Furthermore, the observations in this study may reflect treatment-related immune effects more than those associated with disease.
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PMID:T(H)1/T(H)2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant rheumatoid arthritis and systemic lupus erythematosus patients. 1256 2

Matrix metalloproteinases (MMPs) are endoproteases that have been implicated in the pathogenesis of inflammatory and vasculitic neuropathies. In systemic lupus erythematosus (SLE), a peripheral neuropathy is frequently seen that is thought to be caused by ischemic nerve damage due to vasculopathy and/or vasculitis of the nutritional vessels. However, the exact pathomechanisms causing SLE neuropathy are largely unknown. Elevated MMP levels have been reported in the serum of SLE patients. Supposing that altered expression of MMPs may contribute to vessel wall damage in SLE neuropathy, we investigated the expression of MMP-1, -2, -3, -9, -10 and -13, and their tissue inhibitors (TIMP-1 and -2) in sural nerves from 12 SLE patients in comparison to normal controls. All MMPs could be detected within blood vessel walls from SLE nerves, whereas in controls MMP-3 and MMP-9 was not found. TIMP-1 and TIMP-2, on the other hand, were not informative. Generally, small and large nutritional vessels in the epineurium were immunoreactive for MMPs and TIMPs. Mononuclear cells, which expressed MMP-1, - 3, -10, -13, and TIMP-1 were also observed in most of the SLE nerves, mostly around epineurial blood vessels, but only occasionally in controls. This indicates that expression of MMPs in mononuclear cells may be related to leukocyte trafficking through the vessel walls. However, the density of TIMP-positive and MMP-positive inflammatory cells did not correlate with morphometric parameters regarding the severity of the neuropathy. Our findings suggest that especially the up-regulation of MMP-3 and MMP-9 within the vessel walls may be responsible for the vascular damage seen in SLE and the resulting chronic combined axonal and demyelinating type of neuropathy frequently found in SLE.
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PMID:Peripheral neuropathy in systemic lupus erythematosus: pathomorphological features and distribution pattern of matrix metalloproteinases. 1262 90

Symptoms originating from the central nervous system (CNS) occur frequently in patients with systemic lupus erythematosus (SLE), and CNS involvement in lupus is associated with increased morbidity and mortality. We recently showed that neurones and astrocytes are continuously damaged during the course of CNS lupus. The matrix metalloproteinases (MMPs) are a group of tissue degrading enzymes that may be involved in this ongoing brain destruction. The aim of this study was to examine endogenous levels of free, enzymatically active MMP-2 and MMP-9 in cerebrospinal fluid from patients with SLE. A total of 123 patients with SLE were evaluated clinically, with magnetic resonance imaging of brain and cerebrospinal fluid (CSF) analyses. Levels of free MMP-2 and MMP-9 were determined in CSF using an enzymatic activity assay. CSF samples from another 22 cerebrally healthy individuals were used as a control. Intrathecal MMP-9 levels were significantly increased in patients with neuropsychiatric SLE as compared with SLE patients without CNS involvement (P < 0.05) and healthy control individuals (P = 0.0012). Interestingly, significant correlations between MMP-9 and intrathecal levels of neuronal and glial degradation products were noted, indicating ongoing intrathecal degeneration in the brains of lupus patients expressing MMP-9. In addition, intrathecal levels of IL-6 and IL-8--two cytokines that are known to upregulate MMP-9--both exhibited significant correlation with MMP-9 levels in CSF (P < 0.0001), suggesting a potential MMP-9 activation pathway. Our findings suggest that proinflammatory cytokine induced MMP-9 production leads to brain damage in patients with CNS lupus.
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PMID:Intrathecal levels of matrix metalloproteinases in systemic lupus erythematosus with central nervous system engagement. 1553 33

Atherosclerotic plaque rupture is promoted by metalloproteinase (MMP)-2 and MMP-9, enzymes that degrade the fibrous cap leading to plaque erosion. MMP biosynthesis is mediated by prostaglandin (PG)E2, the product of cyclooxygenase (COX)-2/inducible PGE synthase (mPGES) activity. We have recently reported the overexpression of COX-2/mPGES-1 in vulnerable plaques as a basis of MMP-mediated plaque instability. Hypercholesterolemia and hypertension are two important risk factors for atherosclerosis. Recent trial showed that statins and AT1 receptor blockers significantly reduce the incidence of cardiovascular events in humans. Since anti-inflammatory effects have been reported in association to therapy with statins or AT1 receptor blockers, in two different studies we hypothesized that these drugs can stabilize atherosclerotic plaques through modulation of COX-2/mPGES-1-dependent MMP biosynthesis. Our data demonstrated the stabilizing effect of atherosclerotic plaques by simvastatin or irbesartan, that is due, at least in part, to the reduction of inflammatory burden and suppression of PGE2-dependent metalloproteinases release.
Lupus 2005
PMID:Pharmacological modulation of plaque instability. 1621 85

Matrix metalloproteinases (also named matrixin or MMPs) are a major group of enzymes that regulate cell-matrix composition by using zinc for their proteolytic activities. They are essential for various normal biological processes such as embryonic development, morphogenesis, reproduction tissue resorption, and remodeling. Metalloproteinases also play a role in pathological processes including inflammation, arthritis, cardiovascular diseases, pulmonary diseases and cancer. Herein we review the involvement of MMP-9 in a variety of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, systemic sclerosis, rheumatoid arthritis, multiple sclerosis, polymyositis and atherosclerosis. MMP-9 plays either a primary or secondary role in each one of those autoimmune diseases by its up or down-regulation. It is not expressed constantly but rather is induced or suppressed by many regulating molecules. This feature of MMP-9 along with its involvement in disease pathogenesis turns it into a target for therapy of autoimmune diseases.
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PMID:Matrix metalloproteinase-9 and autoimmune diseases. 1665 30

We investigated the serum concentration of total metalloproteinase-9 (tMPP-9), active MMP-9 (aMMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in a group of 41 patients with SLE and 20 healthy controls. Serum levels of tMMP-9 and TIMP-1 were assessed by an enzyme-linked immunosorbent assay (ELISA) and aMMP-9 by fluorometric assay. The tMMP-9 level was lower in SLE patients (mean 262 ng/mL) than in healthy volunteers (mean 325 ng/mL) (P = .048). Similarly, aMMP-9 level was lower in SLE patients (mean 121 ng/mL) than in control group (mean 169 ng/mL) (P = .0355) and lower in active SLE (mean 54 ng/mL) than in inactive disease (mean 99 ng/mL) (P = .033). TIMP-1 level was also lower in SLE patients (mean 181 ng/mL) than in control group (mean 233 ng/mL) (P = .004). In SLE patients, a positive correlation was found between tMMP-9 and aMMP-9 (rho = 0.568; P = .001). We also found a positive correlation of tMMP-9 and TIMP-1 with VEGF concentrations (rho = 0.450, P = .005 and rho = 0.387; P = .018, resp). tMMP-9, aMMP-9, and TIMP-1 serum levels are lower in SLE patients than in healthy control group.
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PMID:Circulating total and active metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in patients with systemic lupus erythomatosus. 1686 98

To determine risk factors of accelerated atherosclerosis in patients with systemic lupus erythematosus (SLE), 72 patients with inactive disease and 36 age- and sex-matched controls were included. The intima-media thickness (IMT) of the common carotid artery was determined by ultrasound. Traditional risk factors and disease-related factors were recorded. Cardiovascular risk was estimated using SCORE (systematic coronary risk evaluation). Markers of inflammation, endothelial activation and vascular remodelling (matrix metalloproteinases (MMP-3, MMP-9) and tissue inhibitor of metalloproteinase- 1 (TIMP- 1)) were determined. IMT was increased in patients (0.67 mm+/-0.13 versus 0.61 mm+/-0.11, P < 0.05). Prevalence of hypertension (33% versus 6%, P < 0.001), SCORE (2.2 (1.7-4.2) versus 1.7 (1.3-2.1), P < 0.001), as well as parameters of inflammation (CRP 1.8 (0.6-5.8) mg/L versus 0.6 (0.2-1.0) mg/L, P < 0.001) and endothelial activation (VCAM-1 505 (389-683) ng/mL versus 374 (322-427) ng/mL, P < 0.001) and von Willebrand factor (138 (59-208)% versus 48 (24-92)%, P < 0.001), were increased in patients. Vascular remodelling was altered: MMP-3 and TIMP-1 were increased (18 (10-29) ng/mL versus 8 (5-11) ng/mL, P < 0.001, and 275 (216-352) ng/mL versus 230 (197-268) ng/mL, P < 0.001, respectively), and MMP-9 was decreased in SLE (266 (147-412) ng/mL versus 348 (226-530) ng/mL, P < 0.05). Univariate analyses revealed that in patients IMT was associated with age, systolic blood pressure, SCORE and disease duration. In multivariate analysis, age and SCORE were independent predictors of IMT. In conclusion, SLE patients have an increased IMT, which is associated with traditional risk factors. Non-traditional risk factors, such as endothelial activation, altered vascular remodelling and disease duration, might play an additional role.
Lupus 2006
PMID:Traditional and non-traditional risk factors contribute to the development of accelerated atherosclerosis in patients with systemic lupus erythematosus. 1712 May 95

The cellular and molecular mechanisms involved in many abnormalities described in Systemic Lupus Erythematosus (SLE) are still unclear. Some of these abnormalities referred to the hyperactivation of T lymphocytes and the enhanced secretion of MMP-9 by peripheral blood mononuclear cells (PBMCs). Therefore, in this paper we investigated the potential role of CD147 molecule in these abnormalities. Our results demonstrated that CD147 molecule is overexpressed on CD3+T lymphocytes from SLE patients when compared with CD3+T lymphocytes from healthy donors. Monoclonal anti-CD147 antibodies, MEM-M6/1 clone, were able to inhibit protein tyrosine phosphorylation only in CD3 x CD28 costimulated T lymphocytes from SLE patients. However, this monoclonal antibody was unable to inhibit the enhanced activity of MMP-9 secreted by SLE PBMCs.
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PMID:Roles of CD147 on T lymphocytes activation and MMP-9 secretion in systemic lupus erythematosus. 1748 82


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