UNIPROT:P43026 - FACTA Search

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Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) has an established role in the defense against bacterial infections and exerts multiple modulatory activities on both inflammatory and immune responses. However, the relevance of NO on dendritic cell (DC) functions has been poorly investigated. In this study, we found that addition of the NO donor S-nitrosoglutathione (GSNO) to monocyte-derived DCs matured by lipopolysaccharide (LPS) or soluble CD40 ligand led to a decreased capacity to activate naive allogeneic T cells but a more prominent Th1 polarization, with increased interferon-gamma (IFN-gamma) secretion and reduced interleukin-5 (IL-5) release. The presence of GSNO during maturation of DCs caused a reduced expression of surface CD86, whereas CD80, CD83, and MHC molecule expression was not affected. Moreover, GSNO induced a dose-dependent decrease of IL-10 and enhancement of tumor necrosis factor-alpha (TNF-alpha) release from mature DCs. In parallel, a marked reduced production of IL-12 p40 subunit but no significant perturbation of the bioactive IL-12 p70 production was observed. Finally, GSNO significantly reduced the release of IP-10/CXCL10 and RANTES/CCL5 but not IL-8/CXCL8 by mature DCs. Although GSNO can strengthen the capacity of mature DCs to induce type 1 polarization of T lymphocytes, our data suggest that it elicits distinct anti-inflammatory functions, eventually reducing T lymphocyte proliferation and recruitment.
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PMID:Regulatory role of nitric oxide on monocyte-derived dendritic cell functions. 1367 30

Several studies have shown that exposure to bacterial lipopolysaccharide (LPS) can either prevent or inhibit asthma in humans and laboratory rodents. Much emphasis has been placed on the role of cytokines and chemokines in the establishment and maintenance of allergic airway disease. Therefore, it is of interest to study the role of LPS in affecting airway pathology and lung cytokine and chemokine responses in the maintenance phase of asthma. Increasing doses of LPS were administered into the airways of mice presensitized with cockroach allergen (CRAg), then allergic airway disease parameters were assessed after CRAg challenge. Airway hyperresponsiveness after antigen challenge decreased at the highest dose of LPS tested, which was accompanied by a decrease in airway and lung eosinophils. However, a dramatic increase in lung inflammation because of neutrophil influx was observed. Measurement of cytokines in lungs of LPS-treated, CRAg-sensitized mice indicated that interleukin (IL)-12 levels were increased by LPS treatment in a dose-dependent manner, as were levels of several inflammatory chemokines. In contrast, levels of IL-4, IL-13, IL-5, and IL-10 were reduced in whole lung homogenates only of high-dose LPS-treated mice. Intranasal administration of neutralizing anti-IL-12 at the time of high-dose LPS challenge reduced lung IL-12, interferon-gamma, CXCL9, and CXCL10 but did not affect levels of the other chemokines or Th2-type cytokines, and did not restore AHR. These findings suggest that the amelioration of airway hyperresponsiveness observed in LPS-treated, CRAg-sensitized mice is coincident with an immune deviation of the lung inflammatory response, independent of IL-12.
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PMID:Interleukin-12-independent down-modulation of cockroach antigen-induced asthma in mice by intranasal exposure to bacterial lipopolysaccharide. 1457 95

Virus infection, double-stranded RNA, and lipopolysaccharide each induce the expression of genes encoding IFN-alpha and -beta and chemokines, such as RANTES (regulated on activation, normal T cell expressed and secreted) and IP-10 (IFN-gamma inducible protein 10). This induction requires the coordinate activation of several transcription factors, including IFN-regulatory factor 3 (IRF3). The signaling pathways leading to IRF3 activation are triggered by the binding of pathogen-specific products to Toll-like receptors and culminate in the phosphorylation of specific serine residues in the C terminus of IRF3. Recent studies of human cell lines in culture have implicated two noncanonical IkappaB kinase (IKK)-related kinases, IKK-epsilon and Traf family member-associated NF-kappaB activator (TANK)-binding kinase 1 (TBK1), in the phosphorylation of IRF3. Here, we show that purified recombinant IKK-epsilon and TBK1 directly phosphorylate the critical serine residues in IRF3. We have also examined the expression of IRF3-dependent genes in mouse embryonic fibroblasts (MEFs) derived from Tbk1(-/-) mice, and we show that TBK1 is required for the activation and nuclear translocation of IRF3 in these cells. Moreover, Tbk1(-/-) MEFs show marked defects in IFN-alpha and -beta, IP-10, and RANTES gene expression after infection with either Sendai or Newcastle disease viruses or after engagement of the Toll-like receptors 3 and 4 by double-stranded RNA and lipopolysaccharide, respectively. Finally, TRIF (TIR domain-containing adapter-inducing IFN-beta), fails to activate IRF3-dependent genes in Tbk1(-/-) MEFs. We conclude that TBK1 is essential for IRF3-dependent antiviral gene expression.
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PMID:IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts. 1471 69

Astroglia are the most prevalent cell type in the human central nervous system (CNS) and perform important roles in normal tissue homeostasis, during pathological events and following trauma. Astroglial-derived chemokines have important neurotrophic effects and are important to CNS immunocompetence and response to injury, in part, due to their direct role in leukocyte and microglial cell recruitment. However, while ethanol is known to induce CNS pathologies and to be peripherally immunosuppressive, ethanol effects on chemokine expression in human astroglia are essentially unknown. We have demonstrated that chemotaxis of human U937 leukocytic cells, across a 0.5 microm pore polycarbonate transmembrane insert, is induced in response to culture media collected from 10 microg/ml lipopolysaccharide (LPS) + 10 ng/ml interleukin (IL)-1beta-stimulated A172 human astroglia cells. The involvement of the chemokine CXCL10 (also known as interferon-gamma inducible protein or IP-10) in astroglial-induced chemotaxis of U937 cells has been indicated, as chemotaxis can be reduced by an anti-CXCL10 neutralizing antibody. Interestingly, chemotaxis of U937 cells, in response to astroglial-exposed media, is reduced when astroglia are chronically (9 days) exposed to 50 mM ethanol before stimulation with LPS + IL-1beta. Furthermore, we observed that LPS + IL-1beta-stimulated CXCL10 production is inhibited in human A172 astroglia exposed to chronic 50 mM ethanol. Thus, alterations in astroglial CXCL10 expression may disrupt CNS immunocompetence and play an important role in ethanol-induced CNS pathologies.
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PMID:Chronic ethanol inhibits CXC chemokine ligand 10 production in human A172 astroglia and astroglial-mediated leukocyte chemotaxis. 1515 19

In spite of well-known deleterious effects of alcohol on the nervous system in general, its specific effect on the brain immune system remains poorly understood. In order to better understand the effect of alcohol consumption on the innate immunity and inflammatory responses in the central nervous system (CNS), we sought to determine how ethanol influences inflammatory activation of microglia that function as the resident immune defense system of the brain. After treatment of BV-2 mouse microglial cells or rat primary microglia cultures with various stimuli, nitric oxide (NO) production was measured as an indicator of microglial activation. Pretreatment of the cells with ethanol (10-100 mM) for 1 h resulted in a significant decrease in lipopolysaccharide (LPS)-induced, but not interferon-gamma (IFNgamma)-induced, NO production, indicating that ethanol specifically inhibits LPS-induced inflammatory activation of microglia. This was further supported by the ethanol inhibition of LPS-induced IL-1beta expression. In addition, ethanol pretreatment selectively regulated LPS-induced NF-kappaB signaling pathway without affecting IFNgamma-induced signal transducer and activator of transcription 1 (STAT1) phosphorylation, interferon regulatory factor-1 (IRF-1) induction or IFNgamma-inducible IP-10 expression. The modulation of LPS-induced NF-kappaB by ethanol was due to the inhibition of coactivator p300. Altogether, these results suggest that acute ethanol exposure may selectively modulate signal transduction pathways associated with inflammatory activation of microglia, which may lead to derangement of CNS immune and inflammatory responses.
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PMID:Ethanol selectively modulates inflammatory activation signaling of brain microglia. 1546 99

Some chemokines specifically attract T helper 1 (Th1) cells, whereas others attract T helper 2 (Th2) cells. In this study, we investigated the capacity of Langerhans cells (LC) to produce Th1- and Th2-type chemokines in comparison with that of splenic CD11c(+) dendritic cells (DC). We prepared highly purified (>95%) LC from BALB/c mouse skin using the panning method. With regard to Th1-type chemokines, exogenous stimulus, such as interferon-gamma (IFN-gamma), lipopolysaccharide, or polyinosinic-polycytidylic acid, was mandatory for the production of substantial amounts of CXCL10, CXCL9, and CXCL11 both in LC and splenic DC. LC, as a whole, exhibited low ability to produce Th1-type chemokines in comparison with splenic DC. As for Th2-type chemokines, LC, but not splenic DC, produced high levels of CCL22 and CCL17 constitutively during culture even without exogenous stimuli. The production of Th2-type chemokines was regulated in a complicated manner. In particular, interleukin-4 upregulated, and IFN-gamma downregulated both CCL22 and CCL17 production by LC. Of note, LC produced much more amounts of Th2-type chemokines than splenic DC under any conditions tested. Finally, Th1- and Th2-type chemokines produced by LC were shown to be functional using chemokine receptor-transfected-2B4 T cells. The high production of CC chemokine receptor 4 ligands by LC in the absence of IFN-gamma may be an important character discriminating LC from other DC.
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PMID:Differential production of Th1- and Th2-type chemokines by mouse Langerhans cells and splenic dendritic cells. 1567 53

The human P2Y6 receptor (hP2Y6) is a member of the G protein-coupled pyrimidinergic P2 receptor family that responds specifically to the extracellular nucleotide uridine diphosphate (UDP). Recently, the hP2Y6 receptor has been reported to mediate monocyte IL-8 production in response to UDP or lipopolysaccharide (LPS), but the role of hP2Y6 in regulating other pro-inflammatory cytokines or mediators is largely unknown. We demonstrate here that UDP specifically induces soluble TNF-alpha and IL-8 production in a promonocytic U937 cell line stably transfected with hP2Y6. However, we did not detect IL-1alpha, IL-1beta, IL-6, IL-10, IL-18, and PGE2 in the conditioned media from the same cell line. These results distinguish UDP/P2Y6 signaling from LPS signaling. Interestingly, UDP induces the production of IL-8, but not TNF-alpha, in human astrocytoma 1321N1 cell lines stably transfected with hP2Y6. Therefore, the immune effect of UDP/P2Y6 signaling on the production of proinflammatory cytokines is selective and dependent on cell types. We further identify that UDP can also induce the production of proinflammatory chemokines MCP-1 and IP-10 in hP2Y6 transfected promonocytic U937 cell lines, but not astrocytoma 1321N1 cell lines stably transfected with hP2Y6. From the Taqman analysis, UDP stimulation significantly upregulates the mRNA levels of IL-8, IP-10, and IL-1beta, but not TNF-alpha. Taken together, these new findings expand the pro-inflammatory biology of UDP mediated by the P2Y6 receptor.
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PMID:The pyrimidinergic P2Y6 receptor mediates a novel release of proinflammatory cytokines and chemokines in monocytic cells stimulated with UDP. 1579 6

Adjuvants induce the expression of a number of genes in dendritic cells (DCs), which facilitate effective antigen-presentation and cytokine/chemokine liberation. It has been accepted that the toll-like receptor (TLR) family governs the adjuvant activity in DCs. An adjuvant with a long history is mycobacteria in an oil-in-water emulsion, namely Freund's complete adjuvant. Since the active center for the adjuvancy in mycobacteria is the cell-wall skeleton (CWS), we used the bacillus Calmette-Guerin cell-wall skeleton (BCG-CWS) to test DC maturation by GeneChip analysis. We identified the genes supporting an efficient DC response and output. Approximately 2000 genes were up-regulated by BCG-CWS stimulation. BCG-CWS-, peptidoglycan (PGN)- and lipopolysaccharide (LPS)-stimulation generally up-regulated some gene clusters including genes for inflammatory cytokines (TNF, IL1alpha, IL1beta, IL6, IL12 p40, IL23 p19, etc.), chemokines (CCL20, IL8, etc.), cell adhesion molecules (ICAM-1, etc.), apoptosis-related proteins (GADD45B, BCL2A1, etc.), metabolic enzymes (PTGS2, SOD2, etc.) and miscellaneous proteins (EHD1, TNFAIP6, etc.). LPS-stimulation, but not BCG-CWS- or PGN-stimulation, up-regulated the interferon-inducible antiviral proteins, including IFIT1, IFIT2, IFIT4, CXCL10, ISG15, OASL, IFITM1 and MX1. We also found that the BCG-CWS- or PGN-stimulation up-regulated CXCL5, MMP1, etc. We discussed their properties in association with TLRs and recently discovered TLR adapters.
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PMID:Gene-inducing program of human dendritic cells in response to BCG cell-wall skeleton (CWS), which reflects adjuvancy required for tumor immunotherapy. 1586 Feb 29

Intravenous immunoglobulin (IVIG) is involved in many complex mechanisms that act in synergy including expression and function of Fc receptors, complement activation, the cytokine network, interaction with the anti-idiotypic network and modulation of B and T cell activation. To gain insight into the early effects of IVIG on this broad range of activities at the gene level we performed DNA microarray analysis. Human whole blood was incubated in vitro for 4 h followed by extraction of RNA which was hybridized to a chip containing 8793 genes. About 75 upregulated genes and 21 downregulated genes were identified using a cut off for the false discovery rate of 5%. These genes are associated with a wide range of cellular immune functions in line with the broad mechanism of action of IVIG. A striking upregulation of a series of genes coding for chemokines was measured. This finding was confirmed at the protein level as pharmacologically relevant concentrations of CXCL9 and CXCL10 were measured in serum. Interestingly, IVIG shows a partial overlap of its gene expression program with lipopolysaccharide. Our data suggests multiple hypotheses regarding the pharmacology of IVIG that must be validated by complementary studies.
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PMID:Gene expression profiling of the effects of intravenous immunoglobulin in human whole blood. 1604 89

Gender-based differences in the incidence and severity of bacterial sepsis render males more susceptible to septic shock than females. However, the mechanisms that underlie this sexual dimorphism remain unclear. In the present study we confirm that males produce significantly higher levels of the inflammatory cytokine IL-6 and the acute phase protein LPS-binding protein (LBP) than females following in vivo lipopolysaccharide (LPS) exposure. It has also been verified that LPS-challenged male-derived macrophages produce higher levels of IL-1beta and lower levels of PGE(2) than similarly treated female-derived cells. Importantly, we demonstrated that male-derived macrophages produce significantly higher levels of the inflammatory chemokine IP-10 following LPS challenge than their female counterparts. It has been demonstrated further that, although resting macrophage levels of mRNA encoding Toll-like receptor 4 (TLR4) and its co-receptor CD14, are not significantly different between genders, male-derived macrophages constitutively express higher levels of these proteins on their cell surface. Elevated circulating levels of LBP and constitutively higher cell surface expression of TLR4 and CD14 on macrophages in males could result in the observed sexual dimorphism in LPS-induced inflammatory mediator production and the greater susceptibility of males to bacterial sepsis.
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PMID:Sexual dimorphism in expression of receptors for bacterial lipopolysaccharides in murine macrophages: a possible mechanism for gender-based differences in endotoxic shock susceptibility. 1657 44

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