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

This study was undertaken to investigate the capacity of polymorphonuclear neutrophils (PMNs) to secrete Macrophage Inflammatory Protein (MIP)-1alpha and MIP-1beta after stimulation with Porphyromonas endodontalis lipopolysaccharide (LPS). Escherichia coli LPS was used as a positive control. Venous blood was collected and PMNs were isolated from healthy volunteers. Cells were cultured with various concentrations of LPS for different periods of time. Cell supernatants were assayed by enzyme-linked immunosorbent assay. The levels of chemokine secretion in PMNs stimulated with each LPS were found to be significantly higher than in the unstimulated control cells (p < 0.05), and this expression occurred in a time- and dose-dependent manner. E. coli LPS induced higher levels of cytokines than P. endodontalis LPS. These findings demonstrated that P. endodontalis LPS is capable of stimulating PMNs to produce chemotactic cytokines and suggested that PMNs stimulated with P. endodontalis LPS may play a crucial role in the inflammatory and immunopathological reactions of pulpal and periapical diseases.
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PMID:Production of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta by human polymorphonuclear neutrophils stimulated with Porphyromonas endodontalis lipopolysaccharide. 1247 18

CD14 is a receptor important for activation of cells by lipopolysaccharide (LPS). Treatment with the CD14 antibody IC14 was previously found to attenuate the release of proinflammatory cytokines and some chemokines into the circulation of healthy humans intravenously injected with LPS. To determine the role of circulating leukocytes in CD14-dependent gene expression, 16 healthy volunteers received LPS preceded by either IC14 or placebo. At different time points, mRNA was isolated from whole blood and gene expression was determined by multiplex ligation-dependent probe amplification (MLPA). LPS induced MIP-1alpha, MIP-1beta, IL-8, IL-1beta, and IL-1Ra mRNA production, which was delayed by 1 hr and reduced twofold by IC14 treatment. TNFR1 was unresponsive, whereas other investigated cytokines remained undetectable. Further, LPS showed differential effects on NFkappaB gene expression. LPS induced IkappaBalpha production, whereas p50 was unresponsive and p65 and p49/p100 remained undetectable. LPS induced IkappaBalpha expression was delayed (1 hr) and reduced by IC14. Gene expression profiles in blood cells corresponded poorly with observed changes in plasma levels. These data suggest that peripheral blood cells are of negligible importance in LPS-induced production of inflammatory mediators in vivo and that LPS may activate genes via a CD14-independent pathway that is slower and less efficient.
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PMID:Treatment with an anti-CD14 monoclonal antibody delays and inhibits lipopolysaccharide-induced gene expression in humans in vivo. 1275 65

Virulence of the intracellular pathogen Brucella for humans is mainly associated with its lipopolysaccharide (LPS) phenotype, with smooth LPS phenotypes generally being virulent and rough ones not. The reason for this association is not quite understood. We now demonstrate by flow cytometry, electron microscopy, and ELISA that human peripheral blood monocytes interact both quantitatively and qualitatively different with smooth and rough Brucella organisms in vitro. We confirm that considerably higher numbers of rough than smooth brucellae attach to and enter the monocytes in nonopsonic conditions; but only smooth brucellae replicate in the host cells. We show for the first time that rough brucellae induce higher amounts than smooth brucellae of several CXC (GRO-alpha, IL-8) and CC (MIP-1alpha, MIP-1beta, MCP-1, RANTES) chemokines, as well as pro- (IL-6, TNF-alpha) and anti-inflammatory (IL-10) cytokines released by challenged monocytes. Upon uptake, phagosomes containing rough brucellae develop selective fusion competence to form spacious communal compartments, whereas phagosomes containing smooth brucellae are nonfusiogenic. Collectively, our data suggest that rough brucellae attract and infect monocytes more effectively than smooth brucellae, but only smooth LPS phenotypes establish a specific host cell compartment permitting successful parasitism. These novel findings link the LPS phenotype of Brucella and its virulence for humans at the level of the infected host cells. Whether this is due to a direct effect of the LPS molecules or to upstream bacterial mechanisms remains to be established.
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PMID:Smooth and rough lipopolysaccharide phenotypes of Brucella induce different intracellular trafficking and cytokine/chemokine release in human monocytes. 1296 Feb 72

Dendritic cells bridge innate and adaptive immunity and participate in both responses. Upon capture of pathogens, dendritic cells release inflammatory cytokines and chemokines, attracting other immune cells to the infection site. Anti-inflammatory cytokines, glucocorticoids, anti-inflammatory neuropeptides, and lipid mediators such as prostaglandin E2 (PGE2) limit and control the inflammatory response. In this study we report that exogenous PGE2 inhibits CCL3 (MIP-1alpha) and CCL4 (MIP-1beta) expression and release from dendritic cells stimulated with either lipopolysaccharide (LPS), a TLR4 ligand, or peptidoglycan, a TLR2 ligand. The inhibition is dose-dependent and occurs at both the mRNA and protein levels. The inhibitory effect is mediated through EP2 and EP4 receptors and requires the presence of PGE2 at the time of LPS stimulation. Intraperitoneal administration of PGE2 together with LPS results in a reduction in the levels of CCL3 and CCL4 released in the peritoneal fluid, a reduction in the number of dendritic cells accumulating in the peritoneal cavity, and a reduction in CCL3 amount per cell in the peritoneal cell population. These results suggest that one of the mechanisms by which endogenous PGE2 acts as an anti-inflammatory agent, is the inhibition of inflammatory chemokine release from activated dendritic cells, preventing the excess accumulation of activated immune cells.
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PMID:Prostaglandin E2 inhibits production of the inflammatory chemokines CCL3 and CCL4 in dendritic cells. 1296 Feb 84

Modulation of the sialic acid content of cell-surface glycoproteins and glycolipids influences the functional capacity of cells of the immune system. The role of sialidase(s) and the consequent desialylation of cell surface glycoconjugates in the activation of monocytes have not been established. In this study, we show that desialylation of glycoconjugates on the surface of purified monocytes using exogenous neuraminidase (NANase) activated extracellular signal-regulated kinase 1/2 (ERK 1/2), an intermediate in intracellular signaling pathways. Elevated levels of phosphorylated ERK 1/2 were detected in desialylated monocytes after 2 h of NANase treatment, and increased amounts persisted for at least 2 additional hours. Desialylation of cell surface glycoconjugates also led to increased production of interleukin (IL)-6, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta by NANase-treated monocytes that were maintained in culture. Neither increased levels of phosphorylated ERK 1/2 nor enhanced production of cytokines were detected when NANase was heat-inactivated before use, demonstrating the specificity of NANase action. Treatment of monocytes with gram-negative bacterial lipopolysaccharide (LPS) also led to enhanced production of IL-6, MIP-1alpha, and MIP-1beta. The amount of each of these cytokines that was produced was markedly increased when monocytes were desialylated with NANase before exposure to LPS. These results suggest that changes in the sialic acid content of surface glycoconjugates influence the activation of monocytes.
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PMID:Desialylation of glycoconjugates on the surface of monocytes activates the extracellular signal-related kinases ERK 1/2 and results in enhanced production of specific cytokines. 1463 64

To determine the role of CD14 in lipopolysaccharide (LPS)-induced release of chemokines, 16 humans were injected with LPS (4 ng/kg) preceded (-2 h) by intravenous IC14, an anti-human CD14 monoclonal antibody, or placebo. LPS elicited increases in interleukin (IL)-8 concentrations in plasma and in lysates of red blood cell (RBC), polymorphonuclear cell and mononuclear cell fractions, which were all reduced by IC14. LPS also induced rises in the plasma and RBC levels of monocyte chemoattractant protein (MCP)-1, which were diminished by IC14. Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, chemokines that in contrast to IL-8 and MCP-1 can not bind to the Duffy antigen receptor for chemokines on RBCs, were only detected in plasma. IC14 attenuated the LPS-induced release of MIP-1beta, but not of MIP-1alpha. IL-8 and MCP-1, but not MIP-1alpha and MIP-1b, circulate in RBC-associated form during endotoxemia. LPS-induced chemokine release is, in part, mediated by an interaction with CD14.
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PMID:Effect of IC14, an anti-CD14 antibody, on plasma and cell-associated chemokines during human endotoxemia. 1465 90

Interleukin (IL)-15 is a cytokine that has lymphocyte stimulatory activity similar to that of IL-2, and plays important immunoregulatory functions during HIV disease. To evaluate the role of IL-15 in HIV infection the following patients were studied: 18 antiretroviral-naive patients with advanced disease; 19 patients with continuous viral suppression and immunological response after 48-120 weeks of highly active antiretroviral therapy (HAART); and 12 patients with evidence of virological and immunological HAART treatment failure. Nineteen healthy blood donors were included as controls. The production of IL-15 by human peripheral blood monocytes stimulated with lipopolysaccharide and Mycobacterium avium complex, the priming effect of IL-15 on IFN-gamma production from purified CD4(+) and CD8(+) T cells, and the ability of IL-15 to stimulate the beta-chemokine release from purified CD4(+) and CD8(+) T cells were analyzed. In the present work IL-15 production by human peripheral blood monocytes was significantly increased in HIV-infected patients with long-term virological and immunological response to HAART. IL-15 enhanced the in vitro priming of CD4(+) and CD8(+) T cells for IFN-gamma production, also in patients receiving HAART. Finally, IL-15 had positive effects on RANTES, MIP-1alpha, and MIP-1beta release by CD4(+) and CD8(+) T cells. In conclusion IL-15 could affect the immune response of HIV-infected patients by augmenting and/or modulating IFN-gamma production and beta-chemokine release. These data about functional properties of IL-15 could provide new implications for immune-based therapies in HIV infection.
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PMID:Interleukin-15 modulates interferon-gamma and beta-chemokine production in patients with HIV infection: implications for immune-based therapy. 1503 44

Proinflammatory cytokines mediate the toxic effects of superantigenic staphylococcal exotoxins (SE) and bacterial lipopolysaccharide (LPS). Triptolide, an oxygenated diterpene derived from a traditional Chinese medicinal herb, Tripterygium wilfordii, inhibited SE-stimulated T-cell proliferation (by 98%) and expression of interleukin 1beta, interleukin 6, tumor necrosis factor, gamma interferon, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta by human peripheral blood mononuclear cells (PBMC). It also blocked the production of these cytokines and chemokines by LPS-stimulated PBMC in a dose-dependent manner. These results suggest that triptolide has potent immunosuppressive effects even counteracting the effects of superantigens and LPS. It also may be therapeutically useful for mitigating the pathogenic effects of these microbial products by downregulating the signaling pathways activated by both bacterial exotoxins and endotoxins.
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PMID:Triptolide attenuates endotoxin- and staphylococcal exotoxin-induced T-cell proliferation and production of cytokines and chemokines. 1580 59

Phytohemagglutinin (PHA)-induced delayed-type hypersensitivity is an immunocompetent trait considered an indicator of cell-mediated immune or T-cell responses. Divergent selection was performed to generate high and low lines for response to PHA-P. Extreme-responder birds of the F2 generation in each line were used to study possible differences in macrophage activity and the associated functional genes. To evaluate macrophage activity, nitric oxide (NO) was estimated both systemically in serum and in in vitro monocyte culture. Semi-quantitative RT-PCR was used to detect the differential mRNA expression patterns of iNOS and MIP-1beta in monocyte culture, whereas T(H)1 cytokines (IL-2 and IFN-gamma) were studied in peripheral blood mononuclear cells (PBMC) at different time intervals after lipopolysaccharide (LPS) induction. The high line showed strong systemic, as well as in vitro NO production, compared to the low line, upon stimulation with NDV and LPS, similar to early and high iNOS mRNA expression. Following the pattern of iNOS gene expression, an early strong expression of cytokines with powerful iNOS-inducing action, such as IFN-gamma and the chemokine MIP-1beta, was observed in the high line. In contrast, for response to PHA-P, low expression of IL-2 was observed in the high compared to the low line. In conclusion, the study revealed that divergent selection for response to PHA-P resulted in a divergent effect on T(H)1 cell activity, resulting in altered macrophage function in chickens. Selection, based on response to PHA-P, could lead to more resistant birds or birds with an enhanced immune response.
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PMID:Differential expression of inducible nitric oxide synthase and cytokine mRNA in chicken lines divergent for cutaneous hypersensitivity response. 1609 15

To characterize the roles of Porphyromonas gingivalis and its components in disease processes, we investigated the cytokine profiles induced by live P. gingivalis, its lipopolysaccharide (LPS), and its major fimbrial protein, fimbrillin (FimA). A cytokine antibody array revealed that human monocyte-derived macrophages were induced to produce chemokines (e.g., monocyte chemoattractant protein 1, macrophage inflammatory protein 1beta [MIP-1beta], and MIP-3alpha) as early as 1 h after exposure to P. gingivalis, with production declining after 24 h of exposure. As expected, an extensive repertoire of inflammatory mediators increased subsequent to infection, most predominantly tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor. The induction of cytokines by P. gingivalis was not triggered simply by bacterial cell surface components, since purified P. gingivalis LPS and FimA induced similar patterns of cytokines, while the pattern of cytokines induced by live P. gingivalis was significantly different, indicating that the host defense system senses live bacteria differently than it does the cell surface components LPS and FimA. To further understand the mechanisms by which live P. gingivalis and its components exert their effects, we used a high-throughput immunoblot screening approach (Becton-Dickinson PowerBlot) to analyze intracellular proteins involved in P. gingivalis infection in human macrophages. Exposure of human macrophages to either live P. gingivalis, its LPS, or its FimA protein led to the up-regulation of 12, 8, and 10 proteins and the down-regulation of 15, 8, and 17 proteins, respectively. The expression of proteins involved in gene transcription (e.g., monocyte enhancer factor 2D [MEF2D], signal transducer and activator of transcription 1 [STAT1], STAT3, STAT6, and IL enhancer binding factors [ILF3]), of protein kinases (e.g., mitogen-activated protein kinase 3 [MAPK3], MAP3K8, double-stranded RNA-activated protein kinase [PRKR], and MAP2K4), and of proteins involved in immune responses (e.g., TNF super family member 6 [TNFSF6] and interferon-induced protein with tetratricopeptide repeat 4 [IFIT4]), apoptosis (e.g., genes associated with retinoid interferon-induced mortality 19 [GRIM19]), and other fundamental cellular processes (e.g., clathrin heavy-chain polypeptide, culreticulin, and Ras-associated protein RAB27A) was found to be modulated differentially by P. gingivalis, LPS, and FimA. These differential changes are interpreted as preferential signal pathway activation in host immune/inflammatory responses to P. gingivalis infection.
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PMID:Identification of proteins differentially expressed in human monocytes exposed to Porphyromonas gingivalis and its purified components by high-throughput immunoblotting. 1642 70


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