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

The F(1) hybrid of New Zealand Black (NZB) and New Zealand White (NZW) mice develop an autoimmune disease similar to human systemic lupus erythematosus. Because NZB and (NZB x NZW)F(1) mice manifest expansions of marginal zone (MZ) B and B1a cells, it has been postulated that these B cell abnormalities are central to the NZB genetic contribution to lupus. Our previous studies have shown that a major NZB contribution comes from the Nba2 locus on chromosome 1. C57BL/6 (B6) mice congenic for Nba2 produce antinuclear Abs, and (B6.Nba2 x NZW)F(1) mice develop elevated autoantibodies and nephritis similar to (NZB x NZW)F(1) mice. We studied B cell populations of B6.Nba2 mice to better understand the mechanism by which Nba2 leads to disease. The results showed evidence of B cell activation early in life, including increased levels of serum IgM, CD69(+) B cells, and spontaneous IgM production in culture. However, B6.Nba2 compared with B6 mice had a decreased percentage of MZ B cells in spleen, and no increase of B1a cells in the spleen or peritoneum. Expansions of these B cell subsets were also absent in (B6.Nba2 x NZW)F(1) mice. Among the strains studied, B cell expression of beta(1) integrin correlated with differences in MZ B cell development. These results show that expansions of MZ B and B1a cells are not necessary for the NZB contribution to lupus and argue against a major role for these subsets in disease pathogenesis. The data also provide additional insight into how Nba2 contributes to lupus.
 ...
PMID:Separation of the New Zealand Black genetic contribution to lupus from New Zealand Black determined expansions of marginal zone B and B1a cells. 1503 28

CD4(+) T lymphocytes play an important role in the pathogenesis of systemic lupus erythematosus (SLE). To characterize the clonal expansion of CD4(+) T cells in murine lupus models, we analysed the T cell clonality in various organs of young and nephritic MRL/lpr and NZB/W F1 mice using reverse transcription-polymerase chain reaction (RT-PCR) and subsequent single-strand conformation polymorphism (SSCP) analysis. We demonstrated that some identical T cell clonotypes expanded and accumulated in different organs (the bilateral kidneys, brain, lung and intestine) in nephritic diseased mice, and that a number of these identical clonotypes were CD4(+) T cells. In contrast, young mice exhibited little accumulation of common clones in different organs. The T cell receptor (TCR) V beta usage of these identical clonotypes was limited to V beta 2, 6, 8.1, 10, 16 and 18 in MRL/lpr mice and to V beta 6 and 7 in NZB/W F1 mice. Furthermore, some conserved amino acid motifs such as I, D or E and G were observed in CDR3 loops of TCR beta chains from these identical CD4(+) clonotypes. The existence of systemically expanding CD4(+) T cell clones in the central nervous system (CNS) suggests the involvement of the systemic autoimmunity in CNS lesions of lupus. FACS-sorted CD4(+)CD69(+) cells from the kidney displayed expanded clonotypes identical to those obtained from the whole kidney and other organs from the same individual. These findings suggest that activated and clonally expanded CD4(+) T cells accumulate in different tissues of nephritic lupus mice, and these clonotypes might recognize restricted T cell epitopes on autoantigens involved in specific immune responses of SLE, thus playing a pathogenic role in these lupus mice.
 ...
PMID:Identification of systemically expanded activated T cell clones in MRL/lpr and NZB/W F1 lupus model mice. 1514 46

Increased expression of TRAIL in membrane-bound and soluble form in patients with systemic lupus erythematosus (SLE) has been previously reported. In this study, we characterized the upregulation of T-cell-associated and soluble TRAIL (sTRAIL) in vivo and the modulation of TRAIL expression and soluble protein release in vitro following T cell activation and IFNalpha exposure. The expression of membrane-bound TRAIL as determined by flow cytometry was higher on CD4(+) and CD8(+) T cells from lupus patients compared to controls, particularly on activated CD69(+)CD8(+) T cells. Similarly, sTRAIL levels determined by ELISA were significantly elevated in serum from patients with active SLE and correlated with levels of IFNalpha. In vitro, both T-cell-associated and sTRAIL were maximally induced by T cell activation plus IFNalpha in patients and controls. By Western blot analysis, sTRAIL was detected in sera in both the monomeric and multimeric, functional form. Both forms of TRAIL were functional in vitro as determined by Annexin V staining and (51)Cr release assay but the apoptotic activity of membrane TRAIL was 2.5-fold higher compared to that of sTRAIL. These results indicate that IFNalpha-induced enhancement of TRAIL expression and of TRAIL-mediated apoptosis may amplify the abnormal apoptotic process in SLE.
 ...
PMID:Increased expression and release of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by T cells from lupus patients with active disease. 1596 46

Several clinical reports have suggested that prolactin (PRL) plays an important role in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). We have investigated the influence of PRL on immune system, by evaluating the effects of PRL on the expression of CD69 and CD25 on human peripheral blood mononuclear cells (PBMCs). Human PBMCs obtained from healthy female volunteers were incubated with phytohemagglutinin (PHA) in the presence or absence of various concentrations of PRL. The expression of CD69 and CD25 was monitored using immunofluorescence staining and flow cytometry. PRL significantly enhanced the expression of CD69 and CD25 on activated PBMCs compared with that in the absence of PRL (p<0.05, paired t-test). Increasing doses of PRL enhanced the expression of CD69 up to 2 microg/ml and CD25 up to 1 microg/ml. The enhanced expression of CD69 was observed on CD8+ T lymphocytes but not on CD4+ T lymphocytes. Our data suggest that PRL can significantly enhance the expression of CD69 and CD25 molecule on human PBMCs when induced by PHA. However, PRL would have to be at optimal concentration in order to enhance their expression.
 ...
PMID:Enhanced expression of CD69 and CD25 antigen on human peripheral blood mononuclear cells by prolactin. 1628 45

The exact aetio-pathogenesis of systemic lupus erythematosus (SLE) is still speculative, where dysregulation or depletion of CD4+CD25+ T lymphocytes is among the supposed mechanisms. In this study, we thought to investigate patients with SLE for percentages of CD4+CD25+ T cells in their peripheral blood and to correlate this with their disease activity scores. Twenty-five patients with SLE who fulfilled, at least, four of the revised Criteria of the American College of Rheumatology (ACR) and twenty healthy volunteers participated in this study. Activity of SLE was assessed by SLE disease activity index (SLEDAI) score. Percentages of CD4+CD25+ T-cells were determined by a flowcytometric technique, while recently activated T-cells were analysed by assaying the expression of the T-cell activation marker, CD69. A statistically significant (p = 0.003) reduction of percentage of CD4+CD25+ T cells was observed among patients (mean 7.16+/-4.53 %) when compared with control subjects (mean 11.36+/-4.50 %), while a non-significant (p = 0.475) low expression of CD69 on CD4+ T cells was observed between patients (mean 0.32+/-0.28 %) and control subjects (mean 0.32+/-0.38 %). In addition, no correlation could be detected between percentages of CD4+CD25+ T cells and SLEDAI scores among SLE patients (p=0.079). In conclusion, this study adds some evidence for the role of CD4+CD25+ T cells in the pathogenesis of SLE that may have some future therapeutic applications.
 ...
PMID:Diminished CD4+CD25+ T-lymphocytes in peripheral blood of patients with systemic lupus erythematosus. 1673 36

The F(1) hybrid of autoimmune hemolytic anemia-prone NZB and nonautoimmune NZW strains of mice has been studied as a murine model of systemic lupus erythematosus. Both NZB and F(1) hybrid mice show age-dependent spontaneous activation of peripheral CD4(+) T cells as reflected by the elevated frequencies of CD4(+) T cells positive for CD69 early activation marker. Both strains also show age-dependent abnormal decrease of the frequencies of CD62L(+) naive CD4(+) T cells and/or NTA260(+) memory CD4(+) T cells in the spleen. We studied the multigenic control of these abnormal features of peripheral CD4(+) T cells in (NZB x NZW) F(1) x NZW backcross mice by quantitative trait loci mapping and by association rule analysis. The abnormally elevated frequencies of CD69(+)CD4(+) T cells and decreased frequencies of CD62L(+) naive and/or NTA260(+) memory CD4(+) T cells were under the common genetic control, in which the interaction between MHC and a hitherto unknown locus, designated Sta-1 (spontaneous T-cell activation) on chromosome 12, plays a major role. The allelic effects of these loci likely predispose CD4(+) T cells to the loss of self-tolerance, and are responsible for the accelerated autoimmune phenotypes of (NZB x NZW) F(1) hybrid mice.
 ...
PMID:Genetic control of the spontaneous activation of CD4+ Th cells in systemic lupus erythematosus-prone (NZB x NZW) F1 mice. 1702 31

Dendritic cells (DC) play a dual role in the immune response, participating in its induction, and the maintenance of immune tolerance. The aim of this work was to perform a quantitative and phenotypic analysis of DC generated in vitro in the presence of IL-10 in patients with systemic lupus erythematosus (SLE). Blood samples were obtained from 10 active and untreated patients with SLE and six controls. Monocyte-derived DC were generated in vitro in the presence or absence of IL-10, and a quantitative and phenotypic analysis was performed. We found that freshly isolated monocytes from SLE patients had an increased expression of CD11b. On the other hand, the efficiency of in vitro DC generation was diminished in blood samples from SLE patients for conventional DC, but not for IL-10-treated DC. A diminished expression of HLA-DR, CD9 and CD86 was observed in conventional DC from SLE patients compared with controls. In contrast, enhanced levels of HLA-DR, CD80, CD9 and CD151 tetraspanins, FN1 (a class II MHC-tetraspanin epitope), CD85j/ILT2 and CD69 were detected in IL-10-treated DC from SLE patients. Accordingly, the phenotypic profile of IL-10-treated DC was very different in SLE and controls. However, the synthesis of IL-10 and IL-12 was similar in IL-10-treated and conventional cells in both SLE patients and controls. Our findings on the aberrant phenotype of IL-10-treated DC in SLE and their normal efficiency of in vitro generation may be important for the design of future therapies of this condition based on the administration of DC to induce immune tolerance.
 ...
PMID:Phenotypic analysis of IL-10-treated, monocyte-derived dendritic cells in patients with systemic lupus erythematosus. 1708 24

Interferon (IFN)-alpha is involved in the pathogenesis of systemic lupus erythematosus. Studies in murine lupus models have revealed that type I IFN exerts either a protective effect in MRL/lpr, or can detrimentally impact disease progression, as in NZB/W mice. To understand this paradox, we examined the kinetic global gene expression in pre-autoimmune NZB/W-, MRL/lpr- and normal BALB/c-derived splenic mononuclear cells following ex vivo IFN-alpha treatment. Analysis of IFN-alpha-induced gene expression patterns revealed genes associated with antiproliferative activity of IFN-alpha including CDKN1A, GADD45B, pituitary tumor-transforming 1, SCOTIN, ataxia telangiectasia-mutated homolog and calcyclin-binding protein were upregulated in MRL/lpr and/or BALB/c mice. Of IFN-alpha-induced genes differentially expressed in NZB/W vs BALB/c and MRL/lpr mice at 3 h time point, enhanced expression of CCND1, cyclin D2, matrix metalloproteinase 13 and a panel of cytokines and chemokines and impaired expression of negative inflammatory regulators CD69 and an Src family kinase hemopoietic cell kinase were notable. Interestingly, the splenic mononuclear cells from the NZB/W not MRL/lpr lupus-prone mice at the pre-autoimmune stage before ex vivo IFN-alpha treatment, have increased expression of many known IFN-regulated genes. These results provide a unique genomic view of ex vivo IFN-alpha response in two lupus-prone models, and help to have an insight into the role of IFN-alpha in lupus pathogenesis.
 ...
PMID:Genomic view of IFN-alpha response in pre-autoimmune NZB/W and MRL/lpr mice. 1772 92

The acute toxicity of mercury (Hg) to B cells was studied in the peritoneal cavity of BALB/c mice, a coelomic space where both B-1 and B-2 subsets of B lymphocytes are present. Up to 24 hr after a single in situ Hg injection, the peritoneal cavity became virtually devoid of lymphocytes, particularly of the B-1 subset. Lymphocyte depletion was more severe for B than T cells. This depletion was associated with partial lymphocyte activation (CD69(+)) at 6 hr of treatment and it was due to apoptosis rather than to necrosis. Partial recovery of both B and T cells was observed in the peritoneal cavity 48 hr after the Hg injection. The phenomenon was followed by a second decrease in peritoneal lymphocytes 72 hr after Hg. Neutrophils that entered the peritoneal cavity because of the Hg injection were resistant to apoptosis. No significant changes in lymphocyte number or subpopulation were found in the spleen and thymus of the mice up to 72 hr after the Hg treatment. We concluded that B lymphocytes were severely affected by the toxic effects of Hg. Our data suggest that Hg-induced unbalance in the repertoire of B cells, of the B-1 subset in particular, may result later in the secretion of the high titres of pathogenic autoantibodies that are found in the Hg-induced lupus disorder of BALB/c mice.
 ...
PMID:Acute depletion and recovery of peritoneal B-1 lymphocytes in BALB/c mice after a single injection of mercury chloride. 1784 74

The aim was to explore the role of prolactin (PRL) in the lymphocyte activation process in systemic lupus erythematosus (SLE) patients in an in vitro model. Peripheral blood mononuclear cells (PBMCs) were isolated from SLE patients and healthy individuals. The mRNA for PRL and its receptor obtained by standard techniques, with an appropriate primer, were subjected to polymerase chain reaction (PCR) and visualized. The PBMCs were cultured with (a) medium alone as a negative control, (b) unspecific mitogen as a positive control, (c) PRL alone, (d) mitogen plus PRL, (e) mitogen plus antibody anti-PRL, and (f) mitogen plus a nonrelated antibody. Then CD69 and CD154 were determined by flow cytometry analysis. Twelve inactive and 15 active SLE patients were studied. Twenty-five percent of the active patients displayed hyperprolactinemia. Under basal conditions CD69 expression was associated with disease activity. The PBMCs activated in vitro were capable of producing and secreting PRL, measured by mRNA and Nb2 assay. In a similar way, the mRNA for the PRL receptor was visualized. Cells from SLE patients cultivated with PRL alone did not display increased CD69 and CD154 expression. The addition of PRL to the unspecific stimulated culture does not have an additive effect. In contrast, the addition of antibodies against PRL in order to block the autocrine PRL resulted in a striking reduction of CD69 and CD154 expression.
 ...
PMID:Effect of prolactin on lymphocyte activation from systemic lupus erythematosus patients. 1789 82


<< Previous 1 2 3 4 5 6 Next >>