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)

We explored the ex vivo alteration in the cytokine release of stimulated blood taken from healthy volunteers treated subcutaneously with 480 micrograms granulocyte colony-stimulating factor (G-CSF). In a double-blind, controlled, randomized study with 21 volunteers who received G-CSF once or twice 24 hours apart, we measured lipopolysaccharide (LPS)-inducible release of various cytokines and soluble receptors at different times after treatment. At day 1 after a single dose of G-CSF, mediator release was also initiated with muramyl dipeptide, Staphylococcus aureus enterotoxin A, lipoteichoic acid, streptolysin O, complement factor C5a, phytohemagglutinin, or phorbol myristate acetate. In blood from G-CSF-treated subjects, our major findings were (1) a maximal 12-fold increase in interleukin-1 receptor antagonist (IL-1ra) release and an increase of both the p55 and p75 soluble tumor necrosis factor (TNF) receptors; (2) a reduction in TNF release when using all the various stimuli described except LPS; (3) an increase in G-CSF and, to lesser extent, in IL-6, IL-8, and IL-10 release; and (4) an attenuation of interferon-gamma (IFN-gamma) and granulocyte-macrophage (GM)-CSF release. Our findings demonstrate that the major effect of G-CSF treatment is a change in the responsiveness of blood towards a variety of stimuli, which we interpret as a shift toward an antiinflammatory cytokine response.
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PMID:Effect of granulocyte colony-stimulating factor treatment on ex vivo blood cytokine response in human volunteers. 753 16

To test the hypothesis that nitric oxide (NO) limits endothelial activation, we treated cytokine-stimulated human saphenous vein endothelial cells with several NO donors and assessed their effects on the inducible expression of vascular cell adhesion molecule-1 (VCAM-1). In a concentration-dependent manner, NO inhibited interleukin (IL)-1 alpha-stimulated VCAM-1 expression by 35-55% as determined by cell surface enzyme immunoassays and flow cytometry. This inhibition was paralleled by reduced monocyte adhesion to endothelial monolayers in nonstatic assays, was unaffected by cGMP analogues, and was quantitatively similar after stimulation by either IL-1 alpha, IL-1 beta, IL-4, tumor necrosis factor (TNF alpha), or bacterial lipopolysaccharide. NO also decreased the endothelial expression of other leukocyte adhesion molecules (E-selectin and to a lesser extent, intercellular adhesion molecule-1) and secretable cytokines (IL-6 and IL-8). Inhibition of endogenous NO production by L-N-monomethyl-arginine also induced the expression of VCAM-1, but did not augment cytokine-induced VCAM-1 expression. Nuclear run-on assays, transfection studies using various VCAM-1 promoter reporter gene constructs, and electrophoretic mobility shift assays indicated that NO represses VCAM-1 gene transcription, in part, by inhibiting NF-kappa B. We propose that NO's ability to limit endothelial activation and inhibit monocyte adhesion may contribute to some of its antiatherogenic and antiinflammatory properties within the vessel wall.
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PMID:Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. 754 86

Among third-generation cephalosporins, cefodizime (CFDZ) has shown to modulate many functions of the host defense system against infections. The aim of the present study was to assess the in vitro CFDZ-dependent modulation of interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha) and IL-8 release from lipopolysaccharide (LPS)-stimulated human peripheral mononuclear cells (MNCs). Two other third-generation cephalosporins: ceftriaxone (CFX) and ceftazidime (CFT), were also tested under the same experimental conditions. At concentrations ranging from 200 to 50 micrograms/ml, CFDZ significantly decreased TNF-alpha and IL-6 release from maximally (LPS 1 microgram/ml) stimulated MNCs (42% inhibition of TNF-alpha release with 100 micrograms/ml of CFDZ). On the other hand, CFDZ revealed a marked stimulatory effect on IL-8 release (200 micrograms/ml of CFDZ induced 51.5% enhancement of IL-8 release). On the contrary, both CFX and CFT failed to exert any significant effect on TNF-alpha, IL-6 or IL-8 release.
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PMID:Cefodizime modulates in vitro tumor necrosis factor-alpha, interleukin-6 and interleukin-8 release from human peripheral monocytes. 755 10

Commercially available ELISA kits now make it possible to measure cytokines in biological samples and cell culture supernatants. We have compared the levels of IL-1 beta, IL-6, IL-8 and TNF-alpha in various pathological plasma and synovial fluids, and in supernatants of human monocytes activated by lipopolysaccharide (LPS). Measurements were performed using ELISA kits from different companies. A wide variation in values was obtained when measurements were deduced from the standard curves formed with the standard provided by the manufacturers. We also performed calibration curves for all ELISA kits, using the international standards provided by the NIBSC (UK). The coefficients of variation were then significantly improved for IL-6 and IL-8 measurements but not for IL-1 beta and TNF alpha assays. However, despite this attempt to obtain uniform measurements, none of the kits gave similar values for individual samples. These results suggest that the nature of the different pairs of monoclonal antibodies employed in each ELISA does not permit comparable recognition of cytokines in samples. Further work with the various kits is required to establish whether (i) denaturation of the recognized epitope within the natural cytokine, (ii) fragmentation of the cytokine following enzymatic cleavage, (iii) depolymerization, (iv) binding of cytokines to undefined ligands, (v) variable glycosylation of the natural cytokines (vi) recognition of precursor forms, interferes with the measurements.
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PMID:Variable estimates of cytokine levels produced by commercial ELISA kits: results using international cytokine standards. 759 17

Monocytes and retinal pigment epithelial cells are intimately associated in membranes of eyes with proliferative vitreoretinopathy and in certain types of uveitis. The goal of this study was to determine whether monocytes modulate cytokine expression in retinal pigment epithelial cells, and if so, to identify the monocyte products responsible for this effect. Cultured human retinal pigment epithelial cells were exposed to varying concentrations of monocyte-conditioned medium from unstimulated human monocytes for 1-48 hr, or from monocytes prestimulated with lipopolysaccharide. mRNA expression of interleukin-1 beta, interleukin-6, interleukin-8, melanoma growth stimulating activity/gro alpha and gamma, macrophage colony stimulating factor, transforming growth factor-beta 2, basic fibroblast growth factor and activin beta A chain was determined by reverse transcription polymerase chain reaction. Protein secretion of selected cytokines, interleukin-1 beta, interleukin-6, interleukin-8, macrophage colony stimulating factor and transforming growth factor-beta 2 was measured in RPE-conditioned medium by ELISA. Retinal pigment epithelial cells constitutively expressed mRNA for interleukin-6, macrophage colony stimulating factor, transforming growth factor-beta 2, basic fibroblast growth factor and activin beta A chain. Interleukin-1 beta, melanoma growth stimulating activity/gro alpha and gamma and interleukin-8 were not expressed under basal conditions. Stimulated monocyte-conditioned medium markedly induced mRNA of all cytokines except basic fibroblast growth factor and transforming growth factor-beta 2 in a dose- and time-dependent manner. Unstimulated monocyte-conditioned medium was a less potent inducing agent, but still enhanced mRNA expression of interleukin-6, interleukin-8 and melanoma growth stimulating activity/gro alpha. Stimulated monocyte-conditioned medium also induced a time-dependent increase in interleukin-6, Interleukin-8, macrophage colony stimulation factor and transforming growth factor-beta 2, but not interleukin-1 beta protein secretion (p < 0.05 for all time points). Neutralizing antibodies to interleukin-1 beta, or tumour necrosis factor alpha, but not interleukin-1 alpha, significantly reduced cytokine mRNA expression induced by stimulated monocyte-conditioned medium. The combination of all three neutralizing antibodies almost entirely eliminated monocyte-induced mRNA expression and protein production of all cytokines studied. Activated monocytes secrete a heterogeneous mixture of products that together strongly induce expression of multiple cytokines in human retinal pigment epithelial cells. Most if not all of the inducing effect can be accounted for by interleukin-1 beta and tumour necrosis factor alpha. Because cytokines have been implicated in proliferative vitreoretinopathy and uveitis, monocyte-mediated cytokine expression by RPE cells may serve to initiate and perpetuate these diseases.
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PMID:Monocyte-induced cytokine expression in cultured human retinal pigment epithelial cells. 761 19

We investigated the inhibitory effects of a protease inhibitor, FUT-175, on the production of interleukin 8 (IL-8) and polymorphonuclear leukocyte elastase (PMNE) by polymorphonuclear leukocytes (PMN) and vascular endothelial cells. IL-8 production by PMN and vascular endothelial cells stimulated with lipopolysaccharide (LPS) was inhibited by FUT-175. This compound also inhibited PMNE production by PMN following LPS stimulation.
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PMID:Inhibitory effect of FUT-175 on the production of interleukin 8 and polymorphonuclear leukocyte elastase. 762 Aug 20

Neonatal monocytes have diminished function compared with adult cells. The ability to recruit neutrophils through elaboration of chemoattractants has not been evaluated in humans. The pattern of chemoattractant release induced by group B streptococci (GBS) also is unknown. Adult and cord blood monocytes were stimulated with GBS. Supernatants were used as the attractant in blind well chambers; migration to neonatal supernatants was diminished. Interleukin-8 (IL-8) and leukotriene B4 (LTB4) were released in greater quantities by adult monocytes in response to either GBS or lipopolysaccharide. Opsonization of GBS was not required for IL-8 release. Adult monocytes released more LTB4 when stimulated with unopsonized GBS than with opsonized GBS; the neonate's LTB4 production did not increase. IL-8 and LTB4 accounted for the majority of chemoattractant activity released in response to GBS. Decreased production of LTB4 and IL-8 may contribute to the neonate's poor host response to GBS.
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PMID:Group B streptococci elicit leukotriene B4 and interleukin-8 from human monocytes: neonates exhibit a diminished response. 762 84

The effects of Porphyromonas gingivalis lipopolysaccharide (P-LPS) and Escherichia coli lipopolysaccharide (E-LPS) on the gene expression and production of inflammatory cytokines of human periodontal ligament fibroblasts (HPLF) were examined by a Northern (RNA blot) assay and enzyme-linked immunosorbent assay, respectively. mRNAs for interleukin-6 (IL-6), IL-8, and transforming growth factor beta (TGF-beta) were detected in HPLF cells, but IL-1 alpha, IL-1 beta, tumor necrosis factor alpha, transforming growth factor alpha, and granulocyte-macrophage colony-stimulating factor were not detected by reverse transcription-PCR. The expression of TGF-beta mRNA was not influenced by either LPS. P-LPS (1 to 10 micrograms/ml) and E-LPS (100 micrograms/ml) markedly stimulated the expression of IL-6 and IL-8 mRNAs compared with the control. The synthesis of IL-6 and IL-8 was also stimulated by 10 and 100 micrograms of both LPSs per ml, but IL-8 synthesis was not stimulated with E-LPS at 1 microgram/ml. Secretion of IL-6 and IL-8 into the culture medium was detected at 6 and 3 h, respectively, after exposure to P-LPS (10 micrograms/ml). These findings suggested that P. gingivalis leads to periodontal tissue destruction and alveolar bone resorption through IL-6 and IL-8 released from HPLF cells stimulated with its LPS.
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PMID:Inflammatory cytokine gene expression in human periodontal ligament fibroblasts stimulated with bacterial lipopolysaccharides. 764 93

Imiquimod (R-837, S-26308) and the analogue S-27609 were evaluated for cytokine induction in human blood cells. Both compounds induced interferon-alpha (IFN), tumor necrosis factor-alpha (TNF), interleukin (IL)-1 beta, and IL-6 with S-27609 being 5 to 10 times more potent. Imiquimod and S-27609 also induced IL-1 alpha, IL-1 receptor antagonist, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), and macrophage inflammatory protein-1 alpha. The profile of cytokines induced by imiquimod and S-27609 was different from those seen with lipopolysaccharide and polyinosinic-polycytidylic acid. Kinetic studies with both imiquimod and S-27609 revealed induction of cytokines as early as 1-4 h after stimulation. Although most of the cytokines produced by S-27609 were secreted, significant concentrations of IL-1 alpha and IL-1 beta remained intracellular. Monocytes were largely responsible for the cytokines produced. Finally, S-27609-induced mRNA expression for TNF, IFN, and IL-8, and this induction did not require protein synthesis. Taken together, these studies extend previous findings by showing induction of additional cytokines and providing insight into the mechanism of cytokine induction by these molecules.
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PMID:Cytokine induction by the immunomodulators imiquimod and S-27609. 766 93

Interleukin-8 (IL-8) is a major neutrophil chemoattractant and functional stimulant that is induced by IL-1, tumor necrosis factor alpha (TNF alpha), and lipopolysaccharide (LPS). We report that recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) and rhIL-3 are also potent inducers of IL-8 messenger RNA (mRNA) accumulation and protein secretion by normal peripheral blood monocytes. Neutrophils produce IL-8 in response to GM-CSF but not to IL-3. In contrast, recombinant human granulocyte-CSF (rhG-CSF), at concentrations as high as 100 ng/mL, does not induce IL-8 in either cell type. rhGM-CSF also induces IL-8 mRNA expression and IL-8 protein in the promonocytic cell line, U-937, whereas rhG-CSF does not. IL-8 secretion by monocytes was stimulated within 2 hours after incubation with rhGM-CSF or rhIL-3. Stimulation of neutrophils with rhGM-CSF resulted in an increase in cell-associated IL-8 at 4 hours. At 24 hours, cell-associated IL-8 levels declined, whereas secreted IL-8 levels increased. In contrast, virtually all IL-8 induced in monocytes appeared as secreted protein. Neither rhGM-CSF nor rhIL-3 induced detectable secretion of IL-1, TNF alpha, or IL-6 protein by monocytes. rhGM-CSF, and to a lesser degree rhIL-3, potently stimulated IL-8 secretion in cultures of heparinized whole blood, whereas rhG-CSF had no significant effect on IL-8 secretion. Induction of IL-8 by GM-CSF may be physiologically important in enhancing the acute inflammatory response.
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PMID:Effect of granulocyte-macrophage colony-stimulating factor and interleukin-3 on interleukin-8 production by human neutrophils and monocytes. 767 12


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