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)

Our laboratory has recently developed the monoclonal antibody 4F7 which recognizes a molecule on dendritic cells in the dermis of mice that is upregulated after application of contact allergens in vivo. Furthermore, this antibody detects an antigen on dendritic cells in spleen, lymph nodes and colon. In order to study the influence of contact allergens on the surface expression of the 4F7 molecules on dendritic cells, FACScan analysis of splenic dendritic cells was carried out after in vitro application of contact allergens. Freshly isolated splenic dendritic cells were found to be positive for 4F7, 33D1, N418 (CD11c) and MHC class II. After overnight culture the expression of the dendritic cell-specific molecules 4F7 and 33D1 was decreased. This downregulation was not inhibited by the addition of the cytokines TNF-alpha or GM-CSF during in vitro culture. However, in vitro treatment of freshly isolated dendritic cells with the contact allergen 2,4-dinitrofluorobenzene prevented this downregulation of the 4F7 surface molecules. The same effect was observed after treatment with other contact allergens (1-chloro-2,4-dinitrobenzene or potassium dichromate). Treatment with the irritant substance sodium dodecyl sulphate, the lectins concanavalin and lipopolysaccharide or the phorbol ester PMA did not prevent the downregulation of 4F7 and 33D1. Moreover, the influence of contact allergens on the expression of the molecules 4F7 and 33D1 was not inhibited by the protein synthesis inhibitor cycloheximide. No effects of contact sensitizers were detectable on the expression of MHC class II molecules or the costimulatory molecules B7 and heat-stable antigen. Our results show a specific stabilizing effect of contact allergens on the dendritic cell-specific molecules 4F7 and 33D1 independent of de novo protein synthesis.
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PMID:Specific stabilization of the 4F7 molecule on dendritic cells by contact allergens. 895 Apr 54

The kinetics of IL-8, tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta release by PMN adhered to fibronectin, laminin or plastic for 24 h in response to continuous stimulation with lipopolysaccharide (LPS; 50 ng/ml), N-formyl-Met-Leu-Phe (fMLP; 100 mM), or phorbol myristate acetate (PMA; 10 ng/ml), was investigated under altered oxygen tension conditions. Cell supernatants were sampled for cytokine content every 6 h and measured by ELISA. IL-8 was the most abundant cytokine, produced in a range of up to 5.4 ng/ml; TNF-alpha and IL-1 beta were produced in a range of up to 1 ng/ml. During normoxia, LPS was the most potent stimulus, inducing the release of each cytokine, while fMLP showed a less pronounced effect on IL-8 and IL-1 beta production and markedly inhibited TNF-alpha production. PMA markedly suppressed IL-8 and IL-1 beta release and failed to induce any release of TNF-alpha. Hypoxia had an overall inhibitory effect on cytokine release except for PMA-induced IL-1 beta release, and hypoxia/reoxygenation had a significant up-regulating effect except for a further inhibition of fMLP-induced release of TNF-alpha. Integrinmatrix protein ligation differentiated both spontaneous and externally induced cytokine release and its sensitivity to alteration in oxygen tension. Thus the process of PMN elaboration of inflammatory cytokines is controlled on multiple levels of signal transduction, differentiated by integrin-extracellular matrix interactions, and is sensitive to alterations in microenvironmental oxygen tension.
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PMID:Polymorphonuclear leucocyte (PMN)-derived inflammatory cytokines--regulation by oxygen tension and extracellular matrix. 897 28

The molecular basis of the immunotoxic effect of ammonium metavanadate on signal transduction involved in macrophage activation was studied in resident peritoneal macrophages (PEM) and a murine macrophage-like cell line, J774. A fourfold elevation in cytosolic free calcium levels was observed within 10 s following lipopolysaccharide (LPS) stimulation of the non-vanadate-exposed controls both in vitro and in vivo; the levels returned to prestimulation values within 70 s. Exposure to phorbol ester (PMA) did not result in any appreciable change in cytosolic free calcium levels. Compared to untreated controls, treatment with vanadate caused a significant elevation in basal cytosolic calcium levels. Such elevation was not enhanced further by LPS. LPS stimulation of macrophages also resulted in a significant elevation of membrane-associated protein kinase C (PKC) activity, which was, however, inhibited in a dose-dependent manner by vanadate in both in vitro and in vivo studies. Exposure to PMA also resulted in a significant elevation of membrane-associated PKC activity; vanadate treatment at lower levels did not cause downregulation, indicating that vanadate at these levels interfered with the receptor-mediated events rather than the enzyme directly. Vanadate at higher exposure levels inhibited the activity even in PMA-stimulated macrophages. No significant difference occurred in cytosolic PKC activities in control macrophages; vanadate treatment at lower levels resulted in a significant elevation of cytosolic PKC activities following stimulation with LPS or PMA, indicating that vanadate might be interfering with the translocation process.
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PMID:Modulation of macrophage activation by ammonium metavanadate. 897 29

We recently reported that the human monocytic Mono Mac 6sr cell line constitutively takes up and degrades acetylated (acLDL) and oxidized LDL through receptor-specific pathways. The present studies were undertaken to further characterize the acLDL binding site on a functional and molecular basis. The degradation of acLDL increased during differentiation of Mono Mac 6sr cells with lipopolysaccharide (10 ng/mL, 72 hours) and low concentrations of phorbol 12-myristate 13-acetate (PMA; 0.1 to 1.0 ng/mL, 72 hours). Higher doses of PMA (5 or 10 ng/mL), however, decreased acLDL degradation. Scatchard plots of acLDL binding in untreated and LPS-differentiated Mono Mac 6sr cells were nonlinear and suggested the presence of more than one binding site. Although the ligand specificity of the acLDL receptor in Mono Mac 6sr cells resembles that of the macrophage type I and type II scavenger receptors, we did not detect mRNA of either receptor type in untreated or differentiated Mono Mac 6sr cells by means of Northern blotting and reverse transcription polymerase chain reaction. Furthermore, ligand blotting with 125I-acLDL failed to detect the 220-kD types I and II scavenger receptor protein. Thus, Mono Mac 6sr cells express an acLDL receptor that is distinct from the type I and type II scavenger receptor found in human monocyte-derived macrophages but that, like the latter, is induced during monocytic differentiation.
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PMID:Acetylated LDL endocytosis by the human monocytic Mono Mac 6sr cells is not mediated by the macrophage type I and II scavenger receptors. 919 50

Recent studies demonstrate reduced interferon-gamma (IFN-gamma) secretion in neonates who became atopic later in life. The underlying pathomechanism is still unknown. We therefore examined the effects of bacterial products on neonatal IFN-gamma production acting through different T-cell- or antigen-presenting-cell (APC)-stimulating mechanisms: cord-blood mononuclear cells (CBMC) were incubated with lipopolysaccharide (LPS), staphylococcal enterotoxin E (SEE), or a combination of both and restimulated with PMA and ionomycin. LPS and SEE as single stimuli induced IFN-gamma production to the same extent in CBMC of neonates with high and low risk of atopy. In contrast, a combination of LPS and SEE had a multiplying effect on IFN-gamma secretion only in CBMC of neonates with low risk of atopy. Phenotype analysis revealed that only memory T cells showed impaired IFN-gamma synthesis (median 3.6% IFN-gamma-producing cells vs 14.2% in controls: P < 0.01), whereas IFN-gamma production by naive T cells did not differ in either group. Taken together, these results point to the existence of a disturbed function of costimulatory mechanisms in neonates at high risk of atopy, provoking reduced memory T-cell IFN-gamma production.
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PMID:Neonates at risk of atopy show impaired production of interferon-gamma after stimulation with bacterial products (LPS and SEE) 926 83

The regulation of the expression of mouse macrophage elastase (MME) was investigated using the murine tumor cell line P388D1. The effects of three factors were studied: a phorbol ester (4beta-phorbol 12-myristate 13-acetate, PMA), an endotoxin (lipopolysaccharide, LPS) and a corticosteroid (dexamethasone). Both in situ hybridization and northern blot analysis showed that P388D1 cells constitutively express the MME gene. Quantification of the MME mRNA by northern blot analysis showed that only PMA and dexamethasone significantly regulate MME gene expression in a time-dependent and dose-dependent manner. After PMA treatment, the MME mRNA level was maximal between 4 h and 9 h (medium-term response), and the mean amplitude of the response to a concentration of 100 nM was 2.5-fold (P<0.01). LPS did not induce any significant change in MME mRNA level even when 1% serum was added to the cultures. Following dexamethasone treatment, the MME mRNA level was minimal between 21 h and 33 h (long-term response), and the mean amplitude of the response to a concentration of 100 nM was 0.49-fold (P < 0.05). Using actinomycin D, it appeared that the inhibition of RNA synthesis reduces the ulterior stimulating effect of PMA from 184% to 121%, and that MME mRNA has a half-life longer than 8 h, which is not diminished by dexamethasone. These results strongly suggest that the two factors modify MME mRNA level by stimulating (PMA) or inhibiting (dexamethasone) the transcription of the gene, rather than by modifying the transcript stability. Analysis of the cell-conditioned media by elastin zymography showed the MME as a lysis band in the 22-kDa region, the intensity of which varied with the treatments. The MME secretion is stimulated by PMA, inhibited by dexamethasone and does not show any variation after LPS treatment.
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PMID:Metalloelastase expression in a mouse macrophage cell line--regulation by 4beta-phorbol 12-myristate 13-acetate, lipopolysaccharide and dexamethasone. 926 1

Cycloprodigiosin hydrochloride (cPrG.HCl), a member of the prodigiosin family, is a red pigment obtained from the marine bacterium Pseudoalteromonas denitrificans. cPrG.HCl markedly suppressed 3H-thymidine incorporation by concanavalin A stimulated murine splenocytes but had little effect on lipopolysaccharide dependent 3H-thymidine incorporation, indicating that cPrG.HCl acts as a selective inhibitor of T cell proliferation in the same way as other members of the prodigiosin family. cPrG.HCl inhibited the proliferation of the PMA stimulated Jurkat cells through an apoptotic process. Intriguingly, cPrG.HCl inhibited the H+ translocation by vacuolar type ATPase in chromaffin granule membranes without any effect on either its ATPase activity nor on the membrane conductance of phospholipid bilayers, suggesting that cPrG.HCl selectively uncouples H+ translocation from the ATPase reaction rather than acting as a non-specific ionophore. Since crystalline cPrG.HCl is highly stable, it raises the possibility of its therapeutic use as an immunosuppressant.
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PMID:A possible immunosuppressant, cycloprodigiosin hydrochloride, obtained from Pseudoalteromonas denitrificans. 929

Leukaemia inhibitory factor (LIF) acts on the growth and differentiation of haematopoietic cells. By using a specific enzyme-linked immunosorbent assay for human LIF, we demonstrate that human bone marrow stromal cells produce LIF. LIF synthesis is enhanced in a dose-dependent manner after stimulation with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMAS). LIF production in response to PMA is PKC-dependent since the two PKC inhibitors sphingosine and staurosporine markedly diminished it. Interleukin 1alpha (IL-1alpha), IL-1beta, IL-3, IL-6, IL-8, tumour necrosis factor (TNF-alpha) and SCF (both at 10 ng/ml) stimulate LIF production. By contrast macrophage colony-stimulating factor (M-CSF), granulocyte (G)-CSF, GM-CSF, basic fibroblast growth factor (bFGF), platelet-activating factor (PAF), protaglandin E2 (PGE2), leukotriene B4 (LTB4), and leukotriene C4 (LTC4) did not. These results suggest that bone marrow stromal cells might represent a major source for the cytokine-regulated local production of LIF inside human bone marrow.
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PMID:Spontaneous and inducible production of leukaemia inhibitory factor by human bone marrow stromal cells. 934 7

We analyzed the influence of heavy-metal ions on human umbilical vein endothelial cells (HUVEC) in comparison to proinflammatory cytokines (TNF-alpha, IL-1beta) and lipopolysaccharide (LPS). Adhesion molecule and cytokine expressions are upregulated by heavy-metal exposure. Expression of E-selectin on the cell surface was strongly induced by 1-mM concentrations of NiCl2 and CoCl2, whereas ZnCl2 and CrCl3 had no influence. Furthermore, it is shown that NiCl2 induces mRNA expression of E-selectin, intercellular adhesion molecule-1, IL-6 and IL-8 in a 1-mM concentration. The transcription factor NF-kappaB is known to be involved in the regulation of adhesion molecule expression in endothelial cells after activation by proinflammatory cytokines. We demonstrated that treatment of HUVEC with Ni2+ and Co2+ ions induces the translocation of NF-kappaB p65 and also p50 into the nucleus. NF-kappaB binding activity is enhanced under the influence of heavy metals as determined by mobility shift analysis. P65 and p50 are components of the NF-kappaB complexes as confirmed by supershift analysis. We could show that activation at the protein level is accompanied by induction of NF-kappaB p65 mRNA expression. HUVEC also express the NF-kappaB inhibitor I kappaB-alpha (MAD-3). In the early phase of activation by Ni2+ and Co2+ ions, disappearance of I kappaB-alpha in the cytoplasm accompanied p65 translocation, followed by its gradual reappearence. Because I kappaB mRNA could be upregulated by NiCl2 as well as by a mixture of cytokines, we suggest that the replenishment of the inhibitor in the cytoplasm is caused by de novo I kappaB gene expression. In addition to the enhanced DNA-binding activity of NF-kappaB, another transcription factor, AP-1, was also augmented in HUVEC stimulated by NiCl2, CoCl2 or by proinflammatory mediators and the phorbol ester PMA. Fos protein is shown to be a component of the activated AP-1 complex, as determined by supershift analysis, suggesting that it consists of Jun/Fos heterodimers.
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PMID:Heavy metal ion induction of adhesion molecules and cytokines in human endothelial cells: the role of NF-kappaB, I kappaB-alpha and AP-1. 945 94

Oral vomitoxin (VT) exposure in mice results in elevated cytokine gene expression, increased production of IgA, and IgA nephropathy. To determine the potential role of macrophages (Mphi) in these effects, an ex vivo model was devised whereby Peyer's patch (PP) and spleen cells were prepared from mice 2 h after oral exposure to 0 or 25 mg/kg body wt VT, cultured, and then evaluated for IgA and cytokine IL-6 production. Both PP and, to a lesser extent, spleen cells from treatment mice produced more IgA over a 7-day period than did corresponding control cells when cultured without a costimulus or in the presence of either phorbol myristate acetate plus ionomycin (PMA + ION) or lipopolysaccharide (LPS); IgA elevation was most marked in LPS-treated cultures. The VT effect was completely ablated in PP cultures that were depleted of Mphi but not in Mphi-depleted spleen cultures. VT exposure similarly increased production of IL-6, an important helper factor for IgA secretion, in LPS-stimulated PP and spleen cell cultures. IL-6 production was also ablated by Mphi depletion. A potential costimulatory role for Mphi was further suggested because both IgA and IL-6 production increased when Mphi-depleted PP cells from VT-treated animals were cocultured with peritoneal Mphi from VT-treated animals. Similar effects were observed when an analogous ex vivo approach was used with purified PP B cells and peritoneal Mphi. PP B cells from control animals also secreted elevated levels of IgA when cocultured with splenic CD4(+) cells from VT-treated animals, thus confirming previous studies showing that T cell help also contributes to increased IgA production. Potential roles for soluble mediators and cell contact in this process were suggested when IgA production was measured in cultures of PP cells separated from VT-treated Mphi by a semipermeable membrane. Taken together, these and previous results suggest that Mphi may play a key mechanistic role in elevated IgA production and IgA nephropathy in VT-exposed mice.
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PMID:Role of macrophages in elevated IgA and IL-6 production by Peyer's patch cultures following acute oral vomitoxin exposure. 947 34


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