Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the TNF-alpha activity in culture supernatants of monocytes isolated from the peripheral blood of patients with SLE and of normal individuals. The monocytes from patients with SLE stimulated with silica particles, lipopolysaccharide or Staphylococcus aureus Cowan 1 secreted significantly lower amounts of TNF-alpha than did normal monocytes. A decreased TNF mRNA expression was observed in peripheral blood mononuclear cells stimulated by mitogens from patients with SLE. Furthermore, we examined the effect of recombinant TNF-alpha (rTNF-alpha) on the B cell function in SLE patients. rTNF-alpha inhibited the spontaneous B cell proliferation of SLE, but tended to enhance the normal B cell proliferation. Spontaneous IgM production from SLE B cells was inhibited by rTNF-alpha, but that from normal B cells was not. Spontaneous IgG production was unaffected by rTNF-alpha. Also, rTNF-alpha did not affect the viability of B cells. These findings suggest that an impaired TNF-alpha production and an abnormal B cell response to TNF-alpha play a role in the immunological dysfunction in patients with SLE.
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PMID:Impaired tumour necrosis factor-alpha (TNF-alpha) production and abnormal B cell response to TNF-alpha in patients with systemic lupus erythematosus (SLE). 189 18

Interleukin-1 and tumour necrosis factor-alpha activity by E. coli lipopolysaccharide-triggered monocytes was studied in patients with systemic lupus erythematosus in various stages of activity. Monocytes from both groups of SLE patients produced significantly less tumour necrosis factor-alpha activity than those of age and sex matched healthy controls. However, interleukin-1 activity was only significantly reduced in patients with active stage of the disease. These findings indicate further immunoregulatory disturbances in monocyte function concerning SLE.
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PMID:Defective production of interleukin-1 and tumour necrosis factor-alpha by stimulated monocytes from patients with systemic lupus erythematosus. 263 60

Interleukin-1 (IL-1) is a monocyte product with diverse amplifying effects on immune cell reactions. We have studied 16 untreated SLE patients to determine the production of IL-1 by their monocytes under the stimulus of E. Coli lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) and measured by the capacity of their supernatants to augment normal autologous mixed lymphocyte cultures (AMLR) or to replace accessory cells in Con A-induced proliferation of T lymphocytes. Concurrently, we studied the response of T lymphocytes from these same patients to IL-1 by its capacity to increase the percentage of stable E rosette forming cells and by the enhancement of T cell proliferation in AMLR. Monocytes from SLE patients produced significantly less IL-1 activity than those of age matched controls, regardless of the stimulus (LPS or PMA), as well as of the indicator system. All patients with active disease and seven of the 10 patients with inactive disease had decreased production of IL-1 activity as determined by at least one method. Response of T lymphocytes from SLE patients to IL-1 produced by normal monocytes was also found decreased as compared to normals. This defect was more marked in the T cells from patients with active than in those of patients with inactive disease. These findings indicate that the immunoregulatory disturbance that SLE patients have encompasses monocytes as well as T and B lymphocytes and suggest that the defect is either multicentric or originates in the stem cell.
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PMID:Defective monocyte production of, and T lymphocyte response to, interleukin-1 in the peripheral blood of patients with systemic lupus erythematosus. 622 71

Lymph node and spleen cells of the autoimmune MRL/Mp-lpr/lpr mouse strain spontaneously produce (in the absence of mitogenic stimulation) a factor(s) that induces B cell differentiation. This factor is not produced by the congenic MRL/n mouse strain that lacks the lpr gene or by normal mouse strains. However, lymphoid cells of the B6-lpr/lpr (B6/1) strain also produce a B cell differentiation factor. Although the factor acts on resting B cells, its effect is greatly magnified by activating the B cells with anti-mu or lipopolysaccharide. MRL/l mice begin producing the factor as early as 1 mo of age but levels increase with age and appearance of lymphoproliferation. Cell depletion studies reveal that this factor is produced by T cells of the Lyt-1+2-phenotype. Because of its association with the lpr/lpr genotype, we term this B cell differentiation factor L-BCDF. Functional analysis of L-BCDF reveals that it acts regardless of cell density in culture and in the absence of interleukin 2 (IL-2). In fact, the increase in the production of L-BCDF by MRL/1 T cells with aging occurs concomitantly with a marked decrease in their ability to produce IL-2. No T cell replacing factor activity or B cell growth factor-like activity can be detected in MRL/l-derived supernatants. L-BCDF induces both IgM and IgG synthesis in lipopolysaccharide-activated B cells; however, it has a greater effect on IgG secretion. In particular, the production of IgG1, IgG2a, and IgG2b are markedly enhanced in the presence of L-BCDF. The spontaneous production of L-BCDF by T cells of SLE mice of lpr/lpr genotype suggests an association of this factor with autoimmunity.
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PMID:Identification of a B cell differentiation factor(s) spontaneously produced by proliferating T cells in murine lupus strains of the lpr/lpr genotype. 660 Apr 90

It still remains unclear how anti-phospholipid antibody develops in a specific patient group, however, it is possible that certain microorganism(s) may cause anti-cardiolipin antibody (aCL) development since aCL is frequently detected in patients with Treponema pallidum (TP) and/or other infectious diseases. Accordingly, we conducted an investigation to clarify whether or not anticardiolipin antibody (aCL) and/or lupus anticoagulant (LA) can be induced in rabbits by immunization with Gram-positive or -negative microorganism derivatives, such as lipoteichoic acid, lipopolysaccharide and lipid A. We detected the induction of SLE type-aCL (beta 2GPI-dependent) and LA in some rabbits immunized with lipid A and lipoteichoic acid, thereby suggesting that some microorganisms may contribute to even the production of pathogenic (SLE-type) antiphospholipid antibody.
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PMID:Induction of anticardiolipin antibody and/or lupus anticoagulant in rabbits by immunization with lipoteichoic acid, lipopolysaccharide and lipid A. 911 2

Leukemia inhibitory factor (LIF) exhibits multiple biological activities in various tissues, and we have shown that LIF activates POMC gene transcription in response to immune signals. As higher serum levels of LIF have been reported in septicemia, we measured LIF values in biological fluids by RIA. Immunoreactive LIF was detected in 303 of 428 human serum samples. Circulating LIF detection rates were 69% in acute inflammatory diseases, 83% in chronic inflammatory diseases, 61% in noninflammatory diseases, and 90% in cancer patients. Serum concentrations of human LIF was higher in patients with inflammatory disease than in noninflammatory disease (0.80 +/- 0.10 vs. 0.53 +/- 0.02 ng/mL; P < 0.05) or in cancer patients (0.44 +/- 0.06; P < 0.05). Higher serum human LIF levels were found in septicemia (0.78 +/- 0.14 ng/mL), pneumonia (0.80 +/- 0.10 ng/mL), acute bronchitis (0.88 +/- 0.09 ng/mL), other infections (1.01 +/- 0.17 ng/mL), and systemic lupus erythematosus (SLE; 0.79 +/- 0.06 ng/mL). In 7 septicemia patients, Gram-negative infection was associated with higher LIF levels (1.06 +/- 0.16 ng/mL) than was Gram-positive infection (0.58 +/- 0.14 ng/mL). In patients with acute inflammatory disease, serum LIF levels decreased within several days after hospitalization. To test circulating mouse (m) LIF changes in response to inflammatory stress, lipopolysaccharide (LPS) was injected ip to mice. LPS increased serum mLIF values concordantly with ACTH levels. After i.p. injection of 80 microg LPS, serum mLIF increased by 144% (P < 0.05), 173% (P < 0.05), and 134% at 30, 90, and 120 min respectively. In vitro, however, LPS did not increase ACTH and mLIF secretion from dispersed mouse primary pituitary cells. These results suggest that LIF is an important participant in the pathogenesis of the acute inflammatory response. The elevated serum LIF levels observed in inflammation do not appear to originate from the pituitary.
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PMID:Measurement of leukemia inhibitory factor in biological fluids by radioimmunoassay. 954 56

We investigated the production of IL-2, IFN-gamma, IL-10 and IL-4 by PBMC from 24 patients with SLE and 10 healthy individuals. Basal and mitogen-stimulated (lipopolysaccharide and phytohaemagglutinin (LPS + PHA)) cytokine production was determined in a whole blood assay (WBA). Supernatants were collected and assayed with specific ELISAs. Although the IL-2 and IFN-gamma contents did not differ significantly between patients and controls under both conditions, statistically significant correlations were found between each cytokine and disease activity (SLAM index) after stimulation (respectively, r = 0.501, P = 0.01 and r = 0.631, P = 0.001). PBMC IL-10 production was significantly higher for patients than controls (P = 0.05), but no correlation between IL-10 levels and the SLAM index was obtained. IL-4 production was not statistically different between SLE patients and controls. For stimulated WBAs, the IL-10/IL-2 and IL-10/IFN-gamma ratios were significantly correlated with disease severity (P = 0.02; P = 0.001, respectively). Overall, our data suggest that SLE is characterized by an elevated production of IL-10, reflecting the basal state of activation of the immune system. During exacerbation of SLE, IL-2 and IFN-gamma are synthesized in larger amounts and may cause the tissue damage observed.
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PMID:Th1 (IL-2, interferon-gamma (IFN-gamma)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). 993 41

The thymus of New Zealand black (NZB) mice undergoes premature involution. In addition, cultured thymic epithelial cells from NZB mice undergo accelerated preprogrammed degeneration. NZB mice also have distinctive and well-defined abnormalities of thymic architecture involving stromal cells, defined by staining with monoclonal antibodies specific for the thymic microenvironment. We took advantage of these findings, as well as our large panel of monoclonal antibodies which recognize thymic stroma, to study the induction of apoptosis in the thymus of murine lupus and including changes of epithelial architecture. We studied NZB, MRL/lpr, BXSB/Yaa, C3H/gld mice and BALB/c and C57BL/6 as control mice. Apoptosis was studied both at basal levels and following induction with either dexamethasone or lipopolysaccharide (LPS). The apoptotic cells were primarily found in the thymic cortex, and the frequency of apoptosis in murine lupus was less than 20% of controls. Moreover, all strains of murine lupus had severe abnormalities of the cortical network. These changes were not accentuated by dexamethasone treatment in cultured thymocytes. However, the thymus in murine lupus was less susceptible to LPS-induced apoptosis than control mice. Finally we note that the number of thymic nurse cells (TNC) was lowest in NZB mice. Our findings demonstrate significant abnormalities in the induction of apoptosis and the formation of TNC-like epithelial cells in SLE mice, and suggest that the abnormalities of the thymic microenvironment have an important role in the pathogenesis of murine lupus.
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PMID:Apoptosis and the thymic microenvironment in murine lupus. 1055 Feb 20

Recent studies indicate that normal B cells can be primed to differentiate into two distinct cytokine-secreting effector subsets, Be1 and Be2. The aim of this study was to analyse, for the first time, Be1 and Be2 cells at the single cell level in SLE patients using the recently developed technique of flow cytometry for intracellular cytokines. Peripheral blood mononuclear cells (PBMC) from SLE patients and age- and sex-matched normal controls were cultured for 24 h in the presence or absence of phorbal myristate acetate and ionomycin (PMA/I) or lipopolysaccharide (LPS). The production of type I (IFN-gamma, IL-2) and type 2 (IL-4, IL-5, IL-6, IL-10, IL-13) cytokines by B cells (and IL-10 production by fractionated CD5+ and CD5- B cells) was investigated using an intracellular cytokine staining technique and flow cytometry. In the absence of PMA/I stimulation, the percentage of B cells from SLE patients was significantly lower than those of normal subjects and significantly more SLE B cells spontaneously produced IL-10 than controls. Moreover, CD5+ B cells from SLE patients were enriched for cells with signs of previous in vivo activation and for high levels of IL-10 production. A significant positive correlation was observed between the percentage of IL-10- and IL-6-producing PMA/I-stimulated B cells in SLE patients, but not in controls. There were no significant differences in the production of other cytokines by B cells of SLE patients and normal subjects. In conclusion, a general alteration of type 1 and type 2 cytokine production by B cells is not observed in SLE patients. The role of B cell cytokines in the pathogenesis of SLE appears to be exerted by elevated secretion of in vivo IL-10, which may play an important role in the immune dysregulation observed in SLE patients. Moreover, the cross regulation of IL-10 and IL-6 is disrupted in SLE patients.
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PMID:Assessment of Be1 and Be2 cells in systemic lupus erythematosus indicates elevated interleukin-10 producing CD5+ B cells. 1276 98

Complement activation plays a relevant role in the development of tissue damage under inflammatory conditions, and clinical and experimental observations emphasize its contribution to inflammatory vasculitides. Statins have recently been shown to reduce cardiovascular morbidity independently of plasma cholesterol lowering and in vitro studies support a direct anti-inflammatory action of these drugs. The aim of this study was to verify the in vivo effect of fluvastatin on complement-mediated acute peritoneal inflammation. The effect of oral treatment with fluvastatin was investigated in normo-cholesterolaemic rats that received intraperitoneal injection of either yeast-activated rat serum (Y-act RS) or lipopolysaccharide to induce peritoneal inflammation monitored by the number of PMN recruited in peritoneal fluid washes. In addition, vascular adherence and extravasation of leucocytes were evaluated by direct videomicroscopy examination on mesentery postcapillary venules topically exposed to Y-act RS. The number of PMN in the peritoneal washes of rats treated with fluvastatin was 38% lower than that of untreated animals (P < 0.05) 12 h after LPS injection, and was even lower (56%) in rats treated with Y-act RS already 8 h after injection (P < 0.02). Firm adhesion to endothelium and extravasation of leucocytes evaluated under direct videomicroscopy observation were significantly inhibited in fluvastatin treated rats (77% and 72%, respectively; P < 0.01), 120 min after treatment with Y-act RS. Our results demonstrate that fluvastatin inhibits in vivo complement-dependent acute peritoneal inflammation and suggest a role for statins in preventing the inflammatory flares usually associated with complement activation in chronic diseases, such as SLE or rheumatoid arthritis.
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PMID:Fluvastatin treatment inhibits leucocyte adhesion and extravasation in models of complement-mediated acute inflammation. 1473 44


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