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)

The objective of this work was to determine whether HIV-1 and HIV-2 could be involved in the pathogenesis of systemic lupus erythematosus (SLE). Seventy-five consecutive Caucasian patients with SLE presenting at one institution over a 2-year period were studied. Serum samples were surveyed for anti-HIV-1 antibodies by a commercial ELISA coated with HIV-1-p24. For confirmation, conventional immunoblots were performed with the following antigens: HIV-1-gp41, p31, p24 and p17 (recombinant) and HIV-2-gp36 (synthetic peptide). Additionally, Western blots with HIV-1-gp160, gp120, gp41, p65, p51, p24 and p18 bands were applied. Seventeen (23%) patients exhibited reactivity with HIV-1-p24 in the ELISA, but in the immunoblots and Western blots these sera samples were negative. Patients with SLE may exhibit a reactivity with HIV-1-p24 in the ELISA for HIV infection screening but not in the confirmatory blots. This false-positive reactivity is probably due to molecular mimicry between autoantigens and retroviruses or a contaminant or artefacts in the antigen preparation procedure.
Lupus 1995 Feb
PMID:Lack of relationship between human immunodeficiency virus infection and systemic lupus erythematosus. 776 39

The toxic oil syndrome (TOS) represents an exogenously induced autoimmune disease with acute or chronic symptoms similar to systemic lupus erythematosus or scleroderma. When genetically different mouse strains were exposed to oleic acid anilide (OAA), it was possible to mimic the different syndrome manifestations. The aim of the present study was to examine the role of NF-kappaB/Rel transcription factors in the development of the severe acute wasting disease observed in A/J mice. Within a week of OAA exposure, the A/J, but not B10.S strain, displayed weight loss, cachexia, apathy, reduced activity, and breathing difficulties. In affected A/J mice we observed a marked increase in NF-kappaB activation (p50/p65 dimers) both in splenic T cells and peritoneal macrophages as well as in tissue from aorta and gut. Incubation of splenocytes with OAA in vitro induced a dose-dependent removal of IkappaB-alpha, accompanied by NF-kappaB activation, whereas Sp-1 binding was not affected. Furthermore, we demonstrated the increased expression of the two NF-kappaB target genes IL-6 and IL-1beta in OAA-exposed mice and a transient OAA-induced accumulation of TNFalpha in vitro. This is the first report which implicates NF-kappaB/Rel in acute forms of chemically induced autoimmune-like disease and may serve as a paradigm for the involvement of this transcriptional system in acute processes associated with autoimmunity, suggesting possible avenues of therapeutic intervention.
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PMID:Involvement of nuclear factor-kappaB in a murine model for the acute form of autoimmune-like toxic oil syndrome. 1037 5

Numerous cellular and biochemical abnormalities in immune regulation have been described in patients with systemic lupus erythematosus (SLE), including surface Ag receptor-initiated signaling events and lymphokine production. Because NF-kappa B contributes to the transcription of numerous inflammatory genes and has been shown to be a molecular target of antiinflammatory drugs, we sought to characterize the functional role of the NF-kappa B protein complex in lupus T cells. Freshly isolated T cells from lupus patients, rheumatoid arthritis (RA) patients, and normal individuals were activated physiologically via the TCR with anti-CD3 and anti-CD28 Abs to assess proximal membrane signaling, and with PMA and a calcium ionophore (A23187) to bypass membrane-mediated signaling events. We measured the NF-kappa B binding activity in nuclear extracts by gel shift analysis. When compared with normal cells, the activation of NF-kappa B activity in SLE patients was significantly decreased in SLE, but not in RA, patients. NF-kappa B binding activity was absent in several SLE patients who were not receiving any medication, including corticosteroids. Also, NF-kappa B activity remained absent in follow-up studies. In supershift experiments using specific Abs, we showed that, in the group of SLE patients who displayed undetectable NF-kappa B activity, p65 complexes were not formed. Finally, immunoblot analysis of nuclear extracts showed decreased or absent p65 protein levels. As p65 complexes are transcriptionally active in comparison to the p50 homodimer, this novel finding may provide insight on the origin of abnormal cytokine or other gene transcription in SLE patients.
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PMID:Abnormal NF-kappa B activity in T lymphocytes from patients with systemic lupus erythematosus is associated with decreased p65-RelA protein expression. 1041 75

The fate of the lymphocyte is determined by integration of signals delivered after the binding of antigen to the surface antigen receptor, signals delivered by cytokines that bind to their surface receptors, and signals initiated after the engagement of other surface receptors, known as costimulatory molecules. The summation of this input determines whether the immune cell will become stimulated, ignore the signal (anergy), or die (apoptosis). Antigen-receptor signaling events are abnormal in lupus lymphocytes, manifested by increased calcium responses and hyperphosphorylation of several cytosolic protein substrates. Further down, at the gene transcription level, the activity of the nuclear factor kappaB is decreased. These events are underwritten by defective T cell receptor zeta chain expression, overexpression of the gamma chain of the Fc(epsilon)RI that functions as an alternate of zeta chain, and decreased p65 -Rel A protein that is responsible for the inducible NFkappaB activity. Accumulated research data have enabled us to begin deciphering the molecular basis of the abnormal lupus lymphocyte and may lead to the development of new medicinal treatments for lupus.
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PMID:Immune cell signaling in lupus. 1099 Jan 69

The recent identification of a number of molecular defects in T cells from patients with systemic lupus erythematosus (SLE) has raised expectations for gene replacement therapy as an option in the treatment of these diseases. In this report, we have adapted an electroporation-based technique to transfer successfully DNA to peripheral blood T cells from normal individuals and patients with systemic lupus erythematosus and rheumatoid arthritis. Transfection efficiency, judged by the percentage of live cells expressing green fluorescence after transfection with a pGFP (green fluorescence protein), reached 32 +/- 3% in normal, 13 +/- 3% in SLE, and 17 +/- 13% in RA T cells. The transfection efficiency was slightly higher in CD8+ than in CD4+ cells, and the cells maintained acceptable (75%) viability up to the fourth post-transfection day. SLE T cells have been shown to display low levels of the p65 subunit of the NF-kappaB transcription factor and decreased production of IL-2. Since NF-kappaB contributes to the transcriptional regulation of the IL-2 promoter, the effect of the forced replenishment of p65 on IL-2 transcription was tested. The low level of interleukin-2 promoter activity in SLE T cells increased to normal levels following transfection with cDNA encoding the NF-kappaB p65 subunit. Taken together, these results demonstrate the feasibility of transfection of T cells from SLE patients by electroporation and the reversal of decreased interleukin-2 promoter activity in SLE T cells, and are an early step toward gene therapy as a method of treatment for these individuals.
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PMID:Direct transfer of p65 into T lymphocytes from systemic lupus erythematosus patients leads to increased levels of interleukin-2 promoter activity. 1202 19

Intrinsic defects in macrophage (M(phi)) cytokine production characterize many autoimmune-prone mouse strains. Aberrant levels of IL-12, for example, are produced by M(phi) isolated from young mice prone to lupus (MRL and NZB/W) and diabetes (nonobese diabetic (NOD)) well before the appearance of disease signs. Evaluation of the possible mechanism(s) underlying the abnormal regulation of IL-12 in these strains revealed novel patterns of Rel family protein binding to the unique p40 NF-kappaB site in the IL-12 p40 promoter, whereas binding patterns to Ets and CCAAT enhancer binding protein/beta sites were normal. In particular, the heightened production of IL-12 by NOD M(phi) is associated with elevated levels of the trans-activating p50/c-Rel (p65) complex compared with the nonfunctional p50/p50 dimer. Conversely, the dramatically impaired production of IL-12 by both NZB/W and MRL/+ M(phi) is associated with a predominance of p50/p50 and reduced p50/c-Rel(p65) binding. Mechanistically, the unique pattern seen in the lupus strains reflects elevated p50 and reduced c-Rel nuclear protein levels. In NOD extracts, the level of c-Rel is elevated compared with that in lupus strains, but not when compared with that in normal A/J. However, the extent of c-Rel tyrosine phosphorylation noted in NOD extracts is more than double that seen in any other strain. Levels of p65 were similar in all strains tested. These findings reveal that a common mechanism, involving dysregulation of c-Rel and p50, may be used to determine the aberrant IL-12 levels that have the potential to predispose specific mouse strains to systemic or organ-specific autoimmunity.
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PMID:Aberrant production of IL-12 by macrophages from several autoimmune-prone mouse strains is characterized by intrinsic and unique patterns of NF-kappa B expression and binding to the IL-12 p40 promoter. 1207 91

Systemic lupus erythematosus (SLE) is an autoimmune disease, which predominantly affects females, and causes multiple organ dysfunctions. Recent studies have revealed the underlying immunological abnormalities, especially in lymphocytes from SLE patients. T lymphocytes from SLE patients present abnormalities in T cell receptor (TCR) signaling, for example, decreased expression of TCR zeta chain, PKC theta, and NF-kB p65, decreased PKC dependent protein phosphorylation, impaired translocation of NF-kB p65, decreased production of IL-2 etc. Recently, it is known that reconstitution of deficient TCR zeta chain in T lymphocytes from SLE patients leads to restoration of impaired IL-2 production upon CD3/CD28 stimulation. This time, analysis of abnormal TCR signaling in SLE patients and attempt to correct the impaired IL-2 production by replenishing missing signaling molecules are to be discussed.
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PMID:Attempt to correct abnormal signal transduction in T lymphocytes from systemic lupus erythematosus patients. 1643 47

The aim of this study was to investigate the mechanisms of action of Dihydroarteannuin (DHA), a semi-synthesized agent from the starting material artemisinin extracted from the Chinese Traditional Herbs Artemisia annua, on ameliorating the symptoms of lupus on BXSB mice. The concentration of TNF-alpha in the culture supernatant of the peritoneal macrophages and in the sera of BXSB mice was determined by the ELISA method. NF-kappaB protein expression and translocation were assayed by the EMSA method and laser confocal scanning microscopy method, respectively. IkappaB-alpha and NF-kappaB p65 protein expression were determined by the Western blot method. Renal tissue of the BXSB mice was prepared for assaying inhibitory activity of DHA on NF-kappaB, p65 and IkappaB-alpha protein expression in vivo. The peritoneal macrophages were prepared for analysis inhibitory effects of DHA on translocation of NF-kappaB into nuclear in vitro. We found that DHA strongly reduced the production of TNF-alpha in the culture supernatant of the peritoneal macrophages and in the sera of BXSB mice in vitro or in vivo. The results demonstrated that DHA decreased the expression of NF-kappaB subunit p65 protein and the activation of NF-kappaB in the renal tissue of BXSB mice in vivo. DHA effectively inhibited the nuclear translocation of NF-kappaB in peritoneal macrophages of BXSB mice in vitro. Furthermore, it was demonstrated that the degradation of IkappaB-alpha protein was significantly inhibited by DHA. These observations suggested that the inhibitory effects of DHA on TNF-alpha production may result from the block in the NF-kappaB signaling pathway upstream of IkappaB degradation.
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PMID:Dihydroarteannuin ameliorates lupus symptom of BXSB mice by inhibiting production of TNF-alpha and blocking the signaling pathway NF-kappa B translocation. 1678 36

Increased population with hepatic diseases and apoptosis were found in patients with SLE and implicated in the pathogenesis of SLE. Since cystamine has been demonstrated to be beneficial to NZB/W F1 mice in our previous report, this study intends to investigate the effects of cystamine in liver from NZB/W F1 mice. Decreased apoptosis was detected in liver from NZB/W F1 mice given cystamine as compared to those given PBS by TUNEL and caspase-3 activity assay. Fas-dependent apoptotic proteins including Fas, cleaved caspase-8 and tBid were reduced in liver from NZB/W F1 mice given cystamine as compared to those given PBS. Additionally, the mitochondria-dependent apoptotic proteins including cytochrome c and Apaf-1 were reduced in liver from NZB/W F1 mice given cystamine as compared to those given PBS. Moreover, increased BCL-2 protein was observed in liver from both mice. Notably, increased NF-kappaB protein was detected in liver from NZB/W F1 mice given cystamine as compared to those given PBS. These experimental results suggest the effect of cystamine in reducing apoptosis in liver from NZB/W F1 mice through Fas-dependent and mitochondrial-dependent pathways. The phosphorylation of NF-kappaB (p65) could be a possible mechanism involving anti-apoptotic effects of cystamine in liver from NZB/W F1 mice.
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PMID:Treatment with cystamine reduces apoptosis in liver from NZB/W F1 mice. 1832 51

The involvement of the central nervous system (CNS) or neuropsychosis has been reported in patients with systemic lupus erythematosus (SLE) and considered a major cause of long-standing functional impairment and mortality. However, little is known in the improvement of the brain abnormality in SLE. To investigate the effect and mechanism of cystamine on brain in SLE, NZB/W F1 mice were used as the animal model. Gel zymography, caspase-3 activity assay and Western blots were performed to elucidate the effect of cystamine. Significant reduction of matrix metalloproteinases (MMP)-9/MMP-2 ratio and urokinase-type plasminogen activator (uPA) expression was detected in brain of NZB/W F1 mice treated with cystamine as compared to control group. Significant increase of heat-shock protein (HSP)-70 and HSP27 was detected in brain of NZB/W F1 mice treated with cystamine as compared to control group. Additionally, significant reduction of mitochondrial dependent apoptosis was observed in brain of NZB/W F1 mice treated with cystamine as compared to control group by increasing BCL-2 and reducing caspase-9, Bad, and Apaf-1 expression. Moreover, increased phosphorylated p65 (NF-kappaB) protein was observed in brain of NZB/W F1 mice treated with cystamine as compared to control group. These experimental results firstly demonstrated the beneficial effects of cystamine on brain in NZB/W F1 mice and suggested the therapeutic potential in patients with neuropsychiatric SLE (NP-SLE).
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PMID:Beneficial effects of treatment with cystamine on brain in NZB/W F1 mice. 1862 Oct 44


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