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)

In systemic lupus erythematosus, plasma concentrations of tumor necrosis factor alpha (TNF alpha) and other pro-inflammatory cytokines are elevated and those of transforming growth factor beta (TGF beta) are decreased. TNF alpha prevents lupus nephropathy whereas increased concentration of TGF beta causes glomerulosclerosis. Insulin inhibits TNF alpha and enhances TGF beta production, augments nitric oxide synthesis and blocks superoxide anion generation. Polyunsaturated fatty acids (PUFAs) also have actions similar to insulin. Hence, it is suggested that a combination of insulin (in the form of glucose-insulin-potassium) and PUFAs may be of benefit in lupus and other inflammatory conditions.
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PMID:Hypothesis: can glucose-insulin-potassium regimen in combination with polyunsaturated fatty acids suppress lupus and other inflammatory conditions? 1154 28

Nitric oxide (NO) is synthesized via the oxidation of arginine by a family of nitric oxide synthases (NOS), which are either constitutive (ie. endothelial (ec)NOS and neuronal (nc)NOS) or inducible (iNOS). The production of nitric oxide plays a vital role in the regulation of physiological processes, host defence, inflammation and immunity. Pro-inflammatory effects include vasodilation, oedema, cytotoxicity and the mediation of cytokine-dependent processes that can lead to tissue destruction. Nitric oxide-dependent tissue injury has been implicated in a variety of rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis and osteoarthritis. Conversely, the production of NO by endothelial cell NOS may serve a protective, or anti-inflammatory, function by preventing the adhesion and release of oxidants by activated neutrophils in the microvasculature. In this chapter we describe the multifaceted role of nitric oxide in inflammation and address the potential therapeutic implications of NOS inhibition.
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PMID:The role of nitric oxide in tissue destruction. 1181 24

Systemic lupus erythematosus (SLE) is an inflammatory multisystem disease of unknown etiology with immunologic aberrations. Many studies have shown that genetic and environmental factors are implicated in the development of SLE. Angiotensin-converting enzyme (ACE) affects various immune phenomena through the renin-angiotensin and kallikrein-kininogen systems by creating angiotensin II and inactivating bradykinin. We investigated the correlation between insertion/ deletion polymorphism of the ACE gene and the clinical manifestations of SLE, especially vascular involvement and lupus nephritis. Two-hundred and eleven Korean patients fulfilling the ACR criteria and 114 healthy subjects were enrolled. The ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. The nephritis patients were classified by the WHO classification. In addition, the activity and chronicity index were used to assess the severity of renal involvement. We evaluated vascular involvement by the presence or absence of hypertension, Raynaud's phenomenon, livedo reticularis, antineutrophil cytoplasmic antibody and the SLICC/ACR Damage Index. The gene frequency of ACE gene polymorphism was as follows: II 39 vs 34%, ID 41 vs 50%, DD 20 vs 16% in SLE patients and controls, respectively. There was no difference in genotype frequency between both groups. There were no significant differences between the distribution of ACE gene genotypes and lupus nephritis and its related parameters, including WHO classification, activity index, chronicity index, renal dysfunction and amount of 24 h urinary protein. The ACE genotypes and alleles did not affect the presence of vascular manifestations evaluated, but the frequency of DD genotype was significantly low in SLE patients with Raynaud's phenomenon compared to those without Raynaud's phenomenon (P = 0.002 for ACE ID vs DD and II, OR 2.7, 95% CI 1.43-5.09; P=0.023 for ACE DD vs ID and II, OR 0.33, 95% CI 0.12-0.89). Also skewing from DD to II genotype was noted in patients with anti-Sm antibody compared to those without anti-Sm antibody (P = 0.025 for ACE DD vs ID and II, OR 0.21, 95% CI 0.05-0.93). The onset age of serositis was older in patients with the ID genotype than the others (ID= 34.5+/-10.8, II + DD = 25.6+/-10.2, P= 0.002). Also the onset age of malar rash was older in patients with II genotype than the others (II=26.7+/-8.4, ID+DD=21.3+/-9.0; P=0.021). The patients with I allele showed a significantly higher frequency of serositis (P = 0.022). Taken together, the I/D polymorphisms of ACE gene did not affect susceptibility of SLE, lupus nephritis and the vascular manifestations, including Raynaud's phenomenon, in Korean SLE patients, although the DD genotype was negatively associated with Raynaud's phenomenon among SLE patients. However, it would be valuable to evaluate the role of other genes potentially related to vascular events, such as endothelin, nitric oxide or angiotensin II receptor as well as ACE gene.
Lupus 2002
PMID:Angiotensin-converting enzyme gene polymorphism and vascular manifestations in Korean patients with SLE. 1263 Jul 62

Systemic lupus erythematosus (SLE) is an auto-immune disease in which free radicals, eicosanoids, cytokines and nitric oxide seem to play a major role. An increase in the generation of superoxide anion and excess of interleukin-2 (IL-2), tumour necrosis factor (TNF) and pro-inflammatory eicosanoids and a fall in the production of nitric oxide and anti-oxidants such as superoxide dismutase and glutathione peroxidase seems to occur during the active phase of the disease. Thus, an imbalance in the pro-and anti-inflammatory molecules and a change in the delicate balance between the oxidants and anti-oxidants seems to have a vital role in the pathophysiology of SLE. In addition, a defect in the apoptosis of pro-inflammatory T cells may perpetuate the chronic inflammatory process in SLE. Thus, methods designed to suppress the generation of free radicals. IL-1, IL-2 and TNF and of eicosanoids and augment the concentrations of nitric oxide and anti-oxidants and enhance the apoptotic death of the pro-inflammatory T cells may be benefit in the management of SLE. Recent studies suggest that essential fatty acids and their metabolites, whose levels were found to be low in SLE, may restore the balance between pro- and anti-inflammatory molecules, oxidants and anti-oxidants and induce apoptosis of T cell.
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PMID:Oxidants, anti-oxidants, essential fatty acids, eicosanoids, cytokines, gene/oncogene expression and apoptosis in systemic lupus erythematosus. 1215 50

Mycophenolate mofetil (MMF), an immunosuppressive drug commonly used in organ transplantation, is increasingly being used to treat autoimmune diseases including systemic lupus erythematosus (SLE). Excessive production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of lupus nephritis. We evaluated the effect of MMF on the severity of nephritis and the production of NO in lupus-prone MRL/lpr mice. Eight-week-old female MRL/lpr mice (n = 20) were treated with MMF (100 mg/kg/day) by oral gavage for 12 weeks. Control mice (n = 20) received vehicle on the same schedule. The mice were killed after 12 weeks of treatment. Treatment with MMF significantly decreased the amount of proteinuria, prolonged survival and reduced the histological severity of glomerulonephritis. Urinary nitrite/nitrate excretion in the MMF-treated mice was significantly reduced during the first 8 weeks of treatment. However, by the end of the 12 weeks' treatment period, there was no significant difference between vehicle and MMF-treated mice in terms of urinary nitrite/nitrate excretion, intra-renal production of NO, expression of iNOS protein and induction of iNOS mRNA. We conclude that MMF is effective in attenuating the severity of nephritis in MRL/lpr mice. The beneficial effects of MMF on lupus nephritis during the early phase of the disease might be partly attributed to the inhibition of NO production. The inhibitory effect of MMF on NO production diminishes as the disease progresses. MMF probably has additional, as yet undefined mode of actions to fully account for its beneficial effects on lupus nephritis.
Lupus 2002
PMID:Effect of mycophenolate mofetil on severity of nephritis and nitric oxide production in lupus-prone MRL/lpr mice. 1219 81

To investigate the production mechanism and proinflammatory role of the cytokine interleukin (IL-18) in lupus nephritis, we investigated the plasma concentrations of IL-18 and nitric oxide (NO) and the release of IL-18 and NO from mitogen-activated peripheral blood monomuclear cells (PBMC), in 35 SLE patients with renal disease (RSLE), 37 patients without renal disease (SLE) and 28 sex- and age-matched healthy control subjects (NC). IL-18 and NO concentrations were measured by ELISA and colourimetric non-enzymatic assay, respectively. Gene expressions of IL-18 and IL-18 receptor were analysed by RT-PCR. Plasma IL-18 and NO concentrations were significantly higher in RSLE than NC (both P < 0.01). Elevation of plasma IL-18 in RSLE correlated positively and significantly with SLE -disease activity index and plasma NO concentration (r = 0.623, P < 0.0001 and r = 0.455, P = 0.017, respectively), and the latter also showed a positive and significant correlation with plasma creatinine (r = 0.410, P = 0.034) and urea (r = 0.685, P < 0.0001). There was no significant difference in gene expressions of IL-18 and IL-18 receptor in PBMC among RSLE, SLE and NC. Percentage increase in culture supernatant IL-18 concentration was significantly higher in RSLE than SLE and NC (both P < 0.05). The basal NO release was significantly higher in RSLE than that in SLE and NC (both P < 0.005). IL-18 is therefore suggested to play a crucial role in the inflammatory processes of renal disease in SLE.
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PMID:Elevated production of interleukin-18 is associated with renal disease in patients with systemic lupus erythematosus. 1239 Mar 26

Vascular disease and atherosclerosis are significant clinical features of systemic lupus erythematosus and antiphospholipid syndrome. Oxidation is one of the major factors responsible for atheroma development in this context. Anticardiolipin antibodies seem to play an important role by inducing nitric oxide and superoxide production, resulting in enhanced levels of plasma peroxynitrite, which is a powerful pro-oxidant substance. Furthermore, direct interference of these antibodies with paraoxonase activity, a high-density lipoprotein-related anti-oxidant enzyme, would contribute to the oxidative stress found in these conditions. The accelerated process of atherogenesis found in these diseases can represent a useful model for the study of atherosclerosis in the general population.
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PMID:Oxidative stress in systemic lupus erythematosus and antiphospholipid syndrome: a gateway to atherosclerosis. 1296 25

The role of the nitric oxide (NO) radical in systemic lupus erythematosus (SLE) pathogenesis has been investigated in the present study. The binding characteristics of SLE autoantibodies with native calf thymus DNA, native and NO-modified plasmid DNA were assessed. Binding characteristics and specificity of antibodies were analysed by direct binding and inhibition ELISA, gel retardation assay and quantitative precipitin titration. The data shows preferential binding of SLE autoantibodies to NO-modified plasmid DNA (NO-DNA) in comparison with native plasmid DNA. Inhibition ELISA reiterates the direct binding results. Gel retardation assay further substantiated the enhanced recognition of NO-DNA by anti-DNA autoantibodies. The binding affinity of modified and native plasmid DNA with one of the SLE IgGs was calculated, using the Langmuir plot. The apparent association constant for NO-plasmid DNA was found to be highest, followed by native calf thymus DNA and native plasmid DNA. The results suggest that the NO radical modification of plasmid DNA causes perturbations, resulting in the generation of neo-epitopes, and making it a potential immunogen. The DNA modified with the NO radical may be one of the factors for the induction of circulating SLE anti-DNA autoantibodies.
Lupus 2004
PMID:Role of nitric oxide modified DNA in the etiopathogenesis of systemic lupus erythematosus. 1499 1

There is accumulating evidence that haem oxygenase (HO)-1 plays a protective role in various disorders. The beneficial efficacy of HO-1 induction therapy has been shown in renal diseases such as glomerulonephritis, interstitial nephritis and drug induced nephrotoxicity. However, involvement of HO-1 in the development of autoimmune renal diseases remains uncertain. To assess the clinical efficacy of HO-1 induction therapy for lupus glomerulonephritis, MRL/lpr mice were intraperitoneally injected with 100 micromol/kg hemin, a potent HO-1 inducer, or PBS as controls, once a week from 6 weeks of age to 21-24 weeks-old. We found that treatment with hemin led to a significant reduction of proteinuria and remarkable amelioration of glomerular lesions accompanied by decreased immune depositions. In addition, the circulating IgG anti-double-stranded DNA antibody level was significantly decreased in hemin treated mice when compared with controls. A single intraperitoneal injection with hemin resulted in reduction of inducible nitric oxide synthase expression in the kidney and spleen, and serum interferon-gamma level. Our results suggest that HO-1 induction therapy ameliorates lupus nephritis by suppressing nitric oxide (NO) dependent inflammatory responses and attenuating production of pathogenic autoantibodies.
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PMID:Chemical induction of HO-1 suppresses lupus nephritis by reducing local iNOS expression and synthesis of anti-dsDNA antibody. 1549 32

Atherosclerosis is an inflammatory disorder, and the inflammation associated with systemic lupus erythematosus (SLE) accelerates the development of atherosclerosis. Nitric oxide (NO) is an important mediator of inflammation including the inflammation associated with atherosclerosis and SLE. Endothelial nitric oxide synthase (NOS3)-mediated constitutive expression of NO promotes endothelial integrity and normal vascular function. In contrast, inducible nitric oxide synthase- (NOS2) mediated expression of NO promotes endothelial dysfunction and atherogenesis. Statins appear to have anti-inflammatory properties and reverse many of the deleterious effects associated with NO metabolism in atherosclerosis. Statins augment NOS3 expression and inhibit the induction of NOS2. Therefore, the balance between normal vascular function and atherogenesis may be mediated by differences in the quantity, location, and timing of NO production within vessel walls.
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PMID:The dichotomous role of nitric oxide in the pathogenesis of accelerated atherosclerosis associated with systemic lupus erythematosus. 1557 24


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