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) predominantly affects women, especially those in reproductive age. Genetic contributions to disease susceptibility as well as immune dysregulation, particularly persistent inflammatory responses, are considered essential features. Our aim was to determine whether human umbilical vein endothelial cells (HUVEC) isolated from healthy newborns to women with inactive SLE show inflammation-related abnormalities that might lead to an early development of SLE in the offsprings. HUVEC isolated from six women with inactive SLE were stimulated with 2.5 ng/mL of TNF-alpha and/or physiological and pharmacological doses of 17-I(2) estradiol (E2). Then the expression of VCAM-1, ICAM-1, E-selectin, toll-like receptor-9 (TLR-9), heat shock protein 70 (HSP70) and HSP90 were measured. The concentrations of IL-6, IL-8, and IL-10 were also determined in maternal serum and in TNF-alpha stimulated and non-stimulated HUVEC culture supernatant. HUVEC from children with no family history of autoimmune disease served as controls. Our results showed that in HUVEC from SLE+ mothers, a constitutively low expression of adhesion molecules was enhanced by TNF-alpha treatment. The E2 (1 ng/mL) increased the expression of adhesion molecules but had no effect upon TNF-alpha-treated cells. IL-6 was constitutively higher in SLE+ HUVEC, whereas IL-8 was lower; E2 treatment diminished the latter. The E2 had no effect upon IL-6 and IL-8 secretions in TNF-alpha-treated cells. SLE+ HUVEC showed a disordered cytoskeleton and overexpressed HSP70, HSP90, and TLR-9. Our results indicate that endothelial cells of newborns to SLE+ mothers are in a proinflammatory condition which can be upregulated by estrogens.
Lupus 2008 Dec
PMID:The altered expression of inflammation-related molecules and secretion of IL-6 and IL-8 by HUVEC from newborns with maternal inactive systemic lupus erythematosus is modified by estrogens. 1902 76

Neuropsychiatric disease in systemic lupus erythematosus (NPSLE) is a poorly understood, but potentially fatal, disease manifestation. A pathogenetic role for autoantibodies is suspected, but the mechanism is unclear. Since immune complexes in SLE can stimulate IFN-alpha and there is strong evidence in humans and in mice that IFN-alpha can cause neuropsychiatric manifestations, we asked whether NPSLE patient serum and/or cerebrospinal fluid (CSF) contain abnormally high IFN-alpha-inducing activity. In a bioassay containing plasmacytoid dendritic cells and a source of Ag, NPSLE CSF induced significantly higher IFN-alpha compared with CSF from patients with multiple sclerosis or other autoimmune disease controls. When normalized for IgG concentration, NPSLE CSF was 800-fold more potent at inducing IFN-alpha compared with paired serum due to inhibitors present in serum. Analysis of Ig-deficient patient serum, depletion of IgG from normal serum, as well as addition of purified IgG to NPSLE CSF and serum in the bioassays revealed that one inhibitor was contained within the IgG fraction itself. In addition to IFN-alpha, immune complexes formed by CSF autoantibodies produced significantly increased levels of IFN-gamma-inducible protein 10 (IP-10/CXCL), IL-8, and MCP-1, all of which have been reported to be elevated in CSF from NPSLE patients. Taken together, these findings are consistent with a two-step model of NPSLE whereby CSF autoantibodies bind to Ags released by neurocytotoxic Abs or other brain cell injury, and the resulting immune complexes stimulate IFN-alpha and proinflammatory cytokines and chemokines.
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PMID:Potent induction of IFN-alpha and chemokines by autoantibodies in the cerebrospinal fluid of patients with neuropsychiatric lupus. 1912 63

We have previously reported that TRAIL is upregulated on T cells from patients with lupus and that T cell associated TRAIL enhances autoimmune parameters in a murine model of lupus. Whether TRAIL/TRAIL-R interaction plays a role in organ involvement such as lupus nephritis has not yet been assessed. We demonstrate here that TRAIL, DR4 and DR5 are upregulated in proximal and distal tubules of patients with proliferative lupus nephritis. In vitro, expression of TRAIL, DR4 and DR5 on primary proximal tubular epithelial cells (PTEC) was induced by TNFalpha and IFNgamma. Functionally, TRAIL did not induce apoptosis but rather enhanced the proliferation of PTEC through activation of PI3 kinase/AKT and ERK1/2, increased IL-8 production and upregulated ICAM-1 expression. These data demonstrate that cytokine induced upregulation of TRAIL, DR4 and DR5 in tubules from patients with proliferative lupus nephritis may play a protective role by enhancing PTEC survival while also exerting a proinflammatory effect that may contribute to local inflammation and injury.
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PMID:TRAIL, DR4 and DR5 are upregulated in kidneys from patients with lupus nephritis and exert proliferative and proinflammatory effects. 1934 11

Systemic lupus erythematosus is a chronic, multisystemic, autoimmune disease that may involve the central, peripheral, and autonomic nervous systems and can present with a wide variety of neurological and psychiatric manifestations. In this article, we review the recent literature pertaining to the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE). We searched the PUBMED database with no chronological constraints using the following terms: "neuropsychiatric systemic lupus erythematosus" cross-referenced with the terms "pathogenesis" and "biomarkers" for full-text articles in English. The etiology of NPSLE is as yet unknown, though numerous autoantibodies and cytokines have been suggested as possible mediators. Of the numerous autoantibodies and biomarkers examined, anti-phospholipid, anti-ribosomal P, anti-neuronal, anti-glial fibrillary acidic protein (GFAP), anti-endothelial cell, anti-N-methyl-D: -aspartate (NMDA), microtubule-associated protein 2 (MAP-2), and matrix metalloproteinase-9 (MMP-9) appear to be elevated in patients with NPSLE. Cytokines that may be involved in the pathology of NPSLE include interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, and interferons (IFN)-alpha and -gamma. With continued advances in immunological research, new insights into the pathophysiologic mechanisms of NPSLE may lead to the development of biomarkers and new treatment strategies.
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PMID:Pathogenesis of neuropsychiatric systemic lupus erythematosus and potential biomarkers. 1961 49

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with aberrant activation of T and B lymphocytes for the production of inflammatory cytokines and autoreactive antibodies. Animal studies of SLE have indicated that Toll-like receptors (TLR) are important in the pathogenesis of murine lupus. In the present clinical study, differential protein expressions of TLR-1-9 of monocytes and different lymphocyte subsets from patients with SLE and normal control subjects were determined by flow cytometry. Results showed that the expression of intracellular TLRs (TLR-3, -8, -9) and extracellular TLRs (TLR-1, -2, -4, -5, -6) were elevated in monocytes, CD4(+) T lymphocytes, CD8(+) T lymphocytes and B lymphocytes of SLE patients compared to control subjects (all P < 0.001). Moreover, cell surface expression of TLR-4 on CD4(+) T lymphocytes and CD8(+) T lymphocytes, and TLR-6 on B lymphocytes, were correlated positively with SLE disease activity index (SLEDAI) (TLR-4 on CD4(+) T lymphocytes and CD8(+) T lymphocytes: r = 0.536, P = 0.04; r = 0.713, P = 0.003; TLR-6 in B lymphocytes: r = 0.572, P = 0.026). In concordance with the above results, there is an observable increased relative induction (%) of inflammatory cytokine interleukin (IL)-1beta, IL-6, IL-10 and IL-12, chemokines CCL2, CXCL8, CCL5 and CXCL10 from peripheral blood mononuclear cells (PBMC) upon differential stimulation by PolyIC (TLR-3 ligand), lipopolysaccharide (TLR-4 ligand), peptidoglycan (TLR-2 ligand), flagellin (TLR-5 ligand), R837 (TLR-7 ligand) and CpG DNA (TLR-9 ligand) in SLE patients compared to controls. These results suggest that the innate immune response for extracellular pathogens and self-originated DNA plays immunopathological roles via TLR activation in SLE.
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PMID:Activation profile of Toll-like receptors of peripheral blood lymphocytes in patients with systemic lupus erythematosus. 1984 90

Smoking is a central factor in many pathological conditions. Its role in neoplasm, lung and cardiovascular diseases has been well established for years. However it is less acknowledged the cigarette smoking affects both the innate and adoptive immune arms. Cigarette smoke was shown to augment the production of numerous pro-inflammatory cytokines such as TNF-alpha, IL-1, IL-6, IL-8 GM-CSF and to decrease the levels of anti-inflammatory cytokines such as IL-10. Tobacco smoke via multiple mechanisms leads to elevated IgE concentrations and to the subsequent development of atopic diseases and asthma. Cigarette smoke has also been shown activate in many ways macrophage and dendritic cell activity. While it is better evident how cigarette smoke evokes airway diseases more mechanisms are being revealed linking this social hazard to autoimmune disorders, for instance via the production of antibodies recognizing citrullinated proteins in rheumatoid arthritis or by the elevation of anti-dsDNA titers in systemic lupus erythematosus. The current review underlines the importance of smoking prevention and eradication not only in respiratory disorders but also in autoimmune conditions as well.
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PMID:Effects of tobacco smoke on immunity, inflammation and autoimmunity. 2004 14

The pathogenesis of systemic lupus erythematosus (SLE) is far from having been elucidated at the molecular level. Using a multiplex system, we profiled 18 immune mediators in the plasma from 57 patients with SLE. Thirteen of them showed mild to moderate disease activity, and 29 showed severe activity, based upon the SLEDAI score. Fifteen patients were in complete clinical remission. Those patients with active disease, and those in clinical remission had been undergoing immunomodulatory treatment for an average of 10.7 months and 19.2 months respectively at the time of the visit. Samples obtained from 10 healthy volunteers were used as control. Patients with active disease and those with inactive disease showed elevated levels of the chemoattractant proteins MCP-1/CCL2, MIP1-beta/CCL4 and IL-8/CXCL8 as compared to the control (p < 0.05). This pattern of increased mediator levels was observed regardless of the immunomodulatory drug regimen received (non-steroidal anti-inflammatory, steroids or immunosuppressants), and of the degree of tissue damage. Patients with anticardiolipin antibodies (ACAs) showed significantly higher levels of IL-8 and MIP-1beta than those with no ACAs. Levels of MCP-1/CCL2, MIP1-beta/CCL4 and IL-8/CXCL8 correlated significantly, indicating a coordinated regulation of their secretion. Conversely, levels of Th1, Th2, Th17 cytokines, IFN-gamma and growth factors did not differ from those found in the healthy controls. IFN-alpha, IL-1beta, IL-6, IL-7 and IL-13 were undetectable. In conclusion, long term treatment of SLE with standard immunomodulatory drug regimens fails to normalize levels of key chemoattractant proteins linked to innate immunity. This might suggest the existence of a basal, pro-inflammatory state in patients with lupus, even in the absence of symptoms, which could serve as a "substratum" or initiator of the immunological events taking place during a flare-up of the disease.
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PMID:Prolonged standard treatment for systemic lupus erythematosus fails to normalize the secretion of innate immunity-related chemokines. 2014 93

The aims of this study are to investigate the cytokine, chemokine and adhesion molecule profiles in cerebrospinal fluid from patients with neuropsychiatric systemic lupus erythematosus and systemic lupus erythematosus with central nervous system infection. Experimental sets were established which included 108 patients and 132 cerebrospinal fluid samples. The patients were grouped as neuropsychiatric systemic lupus erythematosus (n = 54), systemic lupus erythematosus with central nervous system infection (n = 16), systemic lupus erythematosus controls (n=20), and non-inflammatory neurological disease (n=18). The dynamic changes of 21 patients in the neuropsychiatric systemic lupus erythematosus group before and after induction therapy were further analyzed. IL-1 beta, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNFalpha, IFN gamma, IP-10, MCP-1, RANTES, VCAM-1, and P-selectin were measured in cerebrospinal fluid samples by using a fluorescent bead-based assay. Cerebrospinal fluid levels of IL-8, MCP-1, P-selectin and VCAM-1 were significantly increased in neuropsychiatric systemic lupus erythematosus compared with systemic lupus erythematosus controls. IL-6, IL-17, IL-8 and VCAM-1 were higher in systemic lupus erythematosus with central nervous system infection than in systemic lupus erythematosus controls. Among systemic lupus erythematosus with central nervous system infection, the IL-6, IL-17, IL-8 and IP-10 levels were higher than those in neuropsychiatric systemic lupus erythematosus. After sufficient induction therapy, IL-8, MCP-1, P-selectin, VCAM-1 and IL-6 in patients with neuropsychiatric systemic lupus erythematosus decreased significantly. Levels of all molecules tested in non-inflammatory central nervous system disease were not different from those of systemic lupus erythematosus controls. From our data, the intrathecal cytokine/chemokine profile is different among patients with neuropsychiatric systemic lupus erythematosus, systemic lupus erythematosus complicated with central nervous system infection and systemic lupus erythematosus controls. IL-8, MCP-1, VCAM-1, P-selectin and IL-6 in cerebrospinal fluid are effective parameters to monitor neuropsychiatric systemic lupus erythematosus disease activity and response to treatment. Significantly elevated IL-17, IL-6, and to a lesser extent, IL-8, favors central nervous system infection in systemic lupus erythematosus.
Lupus 2010 May
PMID:Intrathecal cytokine and chemokine profiling in neuropsychiatric lupus or lupus complicated with central nervous system infection. 2017 68

Accumulation in tissues of post-apoptotic cells is a feature frequently observed in patients with systemic lupus erythematosus and in murine models of systemic autoimmune diseases. One of the endogenous danger molecules released by secondarily necrotic cells is monosodium urate (MSU), which is already established to be the causative agent of gout. Here, we show that MSU is taken up by eosinophils, neutrophils and monocytes in a process involving (a) heat-labile serum factor(s) and divalent cations. The uptake induces the release of the pro-inflammatory cytokines IL-1beta/IL-18/TNFalpha and IL-6/IL-8 by monocytes and PMN, respectively.
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PMID:The uptake by blood-borne phagocytes of monosodium urate is dependent on heat-labile serum factor(s) and divalent cations. 2018 3

Deficiencies in the recognition and engulfment of apoptotic cells have been reported in patients with systemic lupus erythematosus (SLE). If dying cells are not promptly cleared, they undergo secondary necrosis and release nuclear autoantigens. Secondarily necrotic cell-derived material (SNEC) can be generated in vitro employing various methods. SNEC generated by either methods shows similar DNA content, light scatter characteristics, and binding pattern of dead and dying cell ligands and is readily recognized by autoantibodies (AAb) of many patients with SLE. In whole blood, AAb opsonize SNEC and foster its uptake by blood-borne non-professional phagocytes. We observed a significant secretion of the inflammatory cytokines IL-8 and TNF-alpha by phagocytes which had engulfed different types of opsonized SNEC. Phagocytosis of SNEC and the subsequent production of inflammatory cytokines were strongly influenced by the presence of DNA in this prey, since DNase I treatment reduced both the uptake of SNEC and the induction of IL-8 and TNF-alpha production. In conclusion, the proinflammatory phagocytosis by circulating phagocytes of IgG-opsonized cellular remnants fosters systemic inflammation in SLE.
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PMID:IgG opsonized nuclear remnants from dead cells cause systemic inflammation in SLE. 2018 5


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