Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Such developments as the introduction of whole new drug classes, as well as the general increase in pediatric drug trials, have led to a revolution in pediatric rheumatology care. For example, selective cyclooxygenase-2 inhibitors can provide the same symptomatic relief as nonselective nonsteroidal anti-inflammatory agents without the same concerns over significant gastrointestinal toxicity. Biologic agents, notably the tumor necrosis factor inhibitors, have effected dramatic improvements in many patients with severe disease who previously were often significantly disabled. New immunosuppressives, such as mycophenolate mofetil, also have promise for ameliorating systemic lupus and vasculitic conditions, perhaps with reduced toxicity compared with other agents. New strategies for the use of older agents have also been further substantiated, such as intra-articular steroid and alternate-day high-dose steroid in chronic arthritis, and broader use of sulfasalazine. Evidence for the use of these therapies is discussed, as are potential toxicities.
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PMID:New drug therapies for the pediatric rheumatic diseases. 1160 97

The primary objectives of this study were to evaluate the safety and efficacy of the cyclooxygenase-2 inhibitor celecoxib in systemic lupus erythematosus (SLE) patients both with and without a self-reported sulfa drug allergy and to review the literature on the use of nonsteroidal agents in SLE subjects. A retrospective review of medical records was performed for 50 SLE patients seen by a community-based rheumatologist and treated with open label celecoxib in doses of 200-400 mg/day for a period of 1-9 months. A MEDLINE search of all articles pertaining to the use of NSAIDs in patients with SLE since 1966 was undertaken. We noted that, in this cohort of celecoxib-treated SLE patients from an office rheumatology practice, the majority demonstrated some improvement, and little toxicity was observed. SLE patients with self-reported sulfa allergies were not more likely to have adverse reactions to celecoxib than non-sulfa allergic patients. The literature review performed herein reveals that, although NSAID toxicity should be a continuing concern in an SLE population, structural dissimilarities between celecoxib and the sulfonamide antimicrobials may make true cross-allergenicity less likely to be a clinical problem. These results suggest that patients with SLE can be safely and effectively treated with celecoxib; however, further studies are needed to assess the effectiveness and safety of all NSAIDs in SLE.
Lupus 2002
PMID:Celecoxib for systemic lupus erythematosus: case series and literature review of the use of NSAIDs in SLE. 1213 71

Autoimmune T-helper cells drive pathogenic autoantibody production in systemic lupus erythematosus (SLE), but the mechanisms maintaining those T cells are unknown. Autoreactive T cells are normally eliminated by functional inactivation (anergy) and activation-induced cell death (AICD) or apoptosis through death receptor (Fas) signaling. However, mutations in the genes encoding Fas and its ligand (FasL) are rare in classical SLE. By gene microarray profiling, validated by functional and biochemical studies, we establish here that activated T cells of lupus patients resist anergy and apoptosis by markedly upregulating and sustaining cyclooxygenase-2 (COX-2) expression. Inhibition of COX-2 caused apoptosis of the anergy-resistant lupus T cells by augmenting Fas signaling and markedly decreasing the survival molecule c-FLIP (cellular homolog of viral FLICE inhibitory protein). Studies with COX-2 inhibitors and Cox-2-deficient mice confirmed that this COX-2/FLIP antiapoptosis program is used selectively by anergy-resistant lupus T cells, and not by cancer cells or other autoimmune T cells. Notably, the gene encoding COX-2 is located in a lupus-susceptibility region on chromosome 1. We also found that only some COX-2 inhibitors were able to suppress the production of pathogenic autoantibodies to DNA by causing autoimmune T-cell apoptosis, an effect that was independent of prostaglandin E(2) (PGE(2)). These findings could be useful in the design of lupus therapies.
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PMID:Human lupus T cells resist inactivation and escape death by upregulating COX-2. 1499 Oct 50

Prostaglandin E(2) (PGE(2)) can have pro- or anti-inflammatory effects, depending on engagement of different PGE(2) receptor (EP) subtypes. The role of EPs in regulating autoimmune inflammation was studied in the murine arthritis/lupus model induced by pristane. Peritoneal macrophages were isolated (biomagnetic beads) from BALB/c, DBA/1, or C57BL/6 mice treated with pristane (intraperitoneally, 3 months earlier) or thioglycolate (3 days earlier) or with untreated controls. EPs, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) mRNA expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Cells were cultured unstimulated or stimulated with lipopolysaccharide (LPS) or LPS + interferon-gamma in combination with EP subtype-specific agonists. Tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6 production was tested by enzyme-linked immunosorbent assay (culture supernatant) and flow cytometry. TNF-alpha mRNA levels also were examined. High levels of EPs (EP4/2>EP1>EP3), iNOS, and COX-2 mRNA were expressed in peritoneal macrophages from pristane-treated but not untreated or thioglycolate-treated mice (RT-PCR). TNF-alpha production was inhibited 50-70% at 2-24 h by EP4/2 agonists, whereas IL-6 was enhanced up to approximately 220%. TNF-alpha inhibition is mediated partly via the protein kinase A pathway and partly via IL-6. Intracellular TNF-alpha staining was inhibited 20% by EP4/2 agonists. TNF-alpha mRNA levels were inhibited 50-70% at 2-24 h, indicating that TNF-alpha inhibition was partly at the level of transcription. EP1/3 agonists had little effect. Synovial cells from mice with pristane-induced arthritis (DBA/1) also expressed EP2/4, and the EP2/4 agonist inhibited TNF-alpha production. PGE(2) can modulate inflammatory reactions via the EP2/4 receptor through its regulation of TNF-alpha and IL-6. Modification of EP signaling may be a new therapeutic strategy in inflammatory/autoimmune diseases.
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PMID:Prostaglandin E2 receptors EP2 and EP4 are up-regulated in peritoneal macrophages and joints of pristane-treated mice and modulate TNF-alpha and IL-6 production. 1507 56

A new class of drugs, the selective cyclooxygenase-2 (COX-2) inhibitors, or coxibs, have recently been marketed as an alternative to conventional nonsteroidal anti-inflammatory drugs (NSAIDs) on the basis of a lower risk of gastrointestinal side effects. The recent withdrawal of rofecoxib, along with safety concerns about other COX-2 selective inhibitors raises important questions about the cardiovascular toxicity of these drugs. Recently some concerns arose even for a possible cardiotoxicity of nonselective nonsteroidal anti-inflammatory drugs. From data available so far, it seems that coxibs still remain a rational choice for patients with low cardiovascular risk and high gastrointestinal risk. Long-term studies with a cardiovascular endpoint involving both selective and nonselective anti-inflammatory drugs are warranted.
Lupus 2005
PMID:Cardiovascular effects of coxibs. 1621 88

Cyclooxygenase-2 (COX-2) is a key regulatory enzyme in the synthesis of prostanoids associated with trauma and inflammation. Upregulation of COX-2 in human lupus T cells resists anergy and apotosis. We investigated the COX-2 gene for functional variants that may influence susceptibility, clinical outcomes and severity of systemic lupus erythematosus (SLE) in a Korean population. The study included 345 patients with SLE and 400 unrelated healthy controls. Genotyping for the -765G --> C polymorphism of COX-2 was performed by PCR-RFLP analysis. No difference in the distribution of the genotype frequencies between patients and controls was found. COX-2 genotypes were not associated with clinical features except hematologic abnormalities and anti-RNP antibody. We did not detect any association between COX-2 genotype and disease severity in SLE patients. These results suggest that the -765G --> C polymorphism of COX-2 does not play a significant role in the development of SLE in a Korean population. A possible protective effect of the low activity C allele against the production of anti-RNP antibodies merits further investigation.
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PMID:Cyclooxygenase-2 polymorphisms and risk of systemic lupus erythematosus in Koreans. 1687 10

Recently a role of the upregulation ofcyclooxygenase isoforms in renal injury and modulation the severity of the inflammatory reactions is suggested. Cyclooxygenase exists as two isoforms COX-1 and COX-2 which are poorly understood with regard to their roles in renal function. Thereby, the present study was undertaken to ascertain the immunoexpression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in lupus (LMGN) and nonlupus (NLMGN) membranous glomerulopathy and to examine the possible relationship between this immunoexpresion and inflammatory infiltrates. Eleven renal biopsy specimens from patients with class V lupus glomerulopathy and 16 from patients with primary (nonlupus) membranous glomerulopathy were examined by percutaneous renal biopsy. As a control 10 biopsy specimens of the kidneys removed because of trauma were used. In each specimen staining intensity of COX-1 and COX-2 in glomeruli, tubuli, arterioles and interstitial cells were recorded semiquantitatively whereas CD68+ cells, CD3+ cells and CD20+ cells were assessed quantitatively using computer image analysis system. Our study revealed that the mean scores of COX-1 immunoexpression did not differ significantly in all groups investigated whereas immunoexpression of COX-2 in LMGN was significantly stronger as compared with both NLMGN and controls. Moreover, in LMGN a significant positive relationship was noted between COX-2 immunoexpression and CD 68+ cells. In NLMGN and controls the correlations between COX-2 immunoexpression and CD 68+ cells were positive, but they have not reached statistical significance. In conclusion, our findings point that glomerular inflammation in lupus and non-lupus membranous glomerulopathy have different signalling pathways and suggest that in lupus nephritis COX-2 and monocytes/ macrophages but not COX-1 isoform are involved in the inflammatory process.
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PMID:Analysis of renal immunoexpression of cyclooxygenase-1 and cyclooxygenase-2 in lupus and nonlupus membranous glomerulopathy. 1845 55