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)

1. The intracellular transport of leukotriene C4 (LTC4) in hematopoietic cells such as human monocytes is controlled by an ATP dependent carrier encoded by the multidrug resistance protein1 (MRPI) gene whose function can be blocked by the compound MK-571. Since LTs play a major role in control of cytokine expression in monocytes, we questioned whether blocking of the MRPI mediated function by MK-571 might affect cytokine production. 2. MK-571 strongly enhanced IL-6 expression at mRNA and protein level in lipopolysaccharide (LPS) and interleukin-1 (IL-1) stimulated human monocytes giving rise to 2.0+/-0.4 (x+/-s.d.) and 5.7+/-3.5 fold induction of IL-6 protein secretion. The increase in IL-6 secretion was accompanied by an enhanced phosphorylation of p38 but not of c-Jun-N terminal kinase. 3. The involvement of the kinase signalling pathways was further analysed by using SB203580 and PD98059, specific inhibitors of the p38 and ERK1/2 signalling route. MK-571 mediated upregulation of IL-6 in the presence of IL-1 was partially attenuated by SB203580 and PD98059. Electrophoretic mobility shift assays demonstrated that MK-571 did not affect the IL-1 induced DNA binding activity of Activator Protein-1 and Nuclear Factor-kappaB but rather enhanced the transactivational activity of an IL-6 promoter construct. Finally it was shown that the MK-571 mediated effects on IL-6 secretion could not be inhibited by the LT synthesis inhibitor SB203347 or by the anti-oxidant pyrrolidine dithiocarbamate (PDTC). 4. These results indicate that the membrane transporter MRP1 is involved in the regulation of IL-6 expression in activated human peripheral blood monocytes.
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PMID:Interleukin-6 production by activated human monocytic cells is enhanced by MK-571, a specific inhibitor of the multi-drug resistance protein-1. 1038 44

Mice with a null mutation of the gene encoding interferon consensus sequence-binding protein (ICSBP) develop a disease with marked expansion of granulocytes and macrophages that frequently progresses to a fatal blast crisis, thus resembling human chronic myelogenous leukemia (CML). One important feature of CML is decreased responsiveness of myeloid cells to apoptotic stimuli. Here we show that myeloid cells from mice deficient in ICSBP exhibit reduced spontaneous apoptosis and a significant decrease in sensitivity to apoptosis induced by DNA damage. In contrast, apoptosis in thymocytes from ICSBP-deficient mice is unaffected. We also show that overexpression of ICSBP in the human U937 monocytic cell line enhances the rate of spontaneous apoptosis and the sensitivity to apoptosis induced by etoposide, lipopolysaccharide plus ATP, or rapamycin. Programmed cell death induced by etoposide was specifically blocked by peptides inhibitory for the caspase-1 or caspase-3 subfamilies of caspases. Studies of proapoptotic genes showed that cells overexpressing ICSBP have enhanced expression of caspase-3 precursor protein. In addition, analyses of antiapoptotic genes showed that overexpression of ICSBP results in decreased expression of Bcl-X(L). These data suggest that ICSBP modulates survival of myeloid cells by regulating expression of apoptosis-related genes.
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PMID:Regulation of apoptosis in myeloid cells by interferon consensus sequence-binding protein. 1043 Jun 29

We have investigated the role of ATP-sensitive potassium (K(ATP)) channels in an experimental model of a delayed phase of vascular hyporeactivity induced by lipopolysaccharide (LPS) in rats. After 24 h, from LPS treatment, in anaesthetized rats the bolus injection of phenylephrine (PE) produced an increase in mean arterial pressure (MAP) significantly (P<0.05) reduced in LPS-treated rats compared to the vehicle-treated rats. This reduction was prevented by pre-treatment of rats with glibenclamide (GLB), a selective inhibitor of K(ATP) channels. GLB administration did not affect the MAP in vehicle-treated rats but produced an increase of MAP in rats treated with LPS. Cromakalim (CRK), a selective K(ATP) channel opener, produced a reduction of MAP that was significantly (P<0.05) higher in LPS- than in vehicle-treated rats. In contrast, the hypotension induced by glyceryl trinitrate (GTN) in LPS-treated rats was not distinguishable from that produced in vehicle-treated rats. Experiments in vitro were conducted on aorta rings collected from rats treated with vehicle or LPS 24 h before sacrifice. The concentration-dependent curve to PE was statistically (P<0.005) reduced in aorta rings collected from LPS- compared to vehicle-treated rats. This difference was totally abolished by tetraethylammonium (TEA), a non-selective inhibitor of K+ channels. CRK produced a relaxation of PE precontracted aorta rings higher in rings from LPS- than in vehicle-treated rats. GLB inhibited CRK-induced relaxation in both tissues, abolishing the observed differences. In conclusion, our results indicate an involvement of K(ATP) channels to the hyporesponsiveness of vascular tissue after 24 h from a single injection of LPS in rats. We can presume an increase in the activity of K(ATP) channels on vascular smooth muscle cells but we cannot exclude an increase of K(ATP) channel number probably due to the gene expression activation.
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PMID:Involvement of ATP-sensitive potassium channels in a model of a delayed vascular hyporeactivity induced by lipopolysaccharide in rats. 1045 95

1. We have utilized the human monocytic cell line, THP-1, and freshly isolated adherent human monocytes with the compounds pyridoxalphosphate-6-azophenyl-2',4'-disuphonic acid (PPADS), oxidized ATP, and 1-(N, O-bis[5-isoquinolinesufonyll]-N-methyl-L-tyrosyl)-4-phenylpiper azi ne (KN-62) to pharmacologically characterize the P2 receptor involved in ATP-induced release of interleukin 1beta (IL-1beta). We have also investigated the involvement of P2 receptors in lipopolysaccharide (LPS)-induced IL-1beta release from both cell types. 2. ATP caused release of IL-1beta from LPS primed THP-1 cells in both a time- and concentration-dependent manner, with a minimal effective ATP concentration of 1 mM. Stimulation of cells with 5 mM ATP resulted in detectable concentrations of IL-1beta in cell supernatants within 30 min. 3. The ATP analogue benzoylbenzoyl ATP (DBATP), a P2X7 receptor agonist, was approximately 10 fold more potent than ATP at eliciting IL-1beta release. 4. KN-62 (1 micro M), PPADS (100 microM) or oxidized ATP (100 uM) significantly inhibited 5 mM ATP-induced IL-1beta release by 81, 90 and 66% respectively, but failed to significantly inhibit LPS-induced IL-1beta release in both THP-1 cells and in freshly isolated human monocytes. 5. In both THP-1 cells and freshly isolated human monocytes, addition of the ATP degrading enzyme apyrase (0.4 U ml(-1)) to cell supernatants prior to LPS activation failed to significantly inhibit the LPS-induced IL-1beta release. In addition there was no correlation between extracellular ATP concentrations and IL-1beta release in THP-1 cells when studied over a 6 h time period. 6. In conclusion our data confirm the involvement of P2X7 receptors in ATP-induced IL-1beta release in human monocytes. However no evidence was obtained which would support the involvement of either endogenous ATP release or P2X7 receptor activation as the mechanism by which LPS-induces IL-1beta release in either the THP-1 cell line or in freshly isolated human monocytes.
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PMID:Pharmacological characterization of ATP- and LPS-induced IL-1beta release in human monocytes. 1048 24

Brochocin-C is a two-peptide bacteriocin produced by Brochothrix campestris ATCC 43754 that has a broad activity spectrum comparable to that of nisin. Brochocin-C has an inhibitory effect on EDTA-treated gram-negative bacteria, Salmonella enterica serovar Typhimurium lipopolysaccharide mutants, and spheroplasts of Typhimurium strains LT2 and SL3600. Brochocin-C treatment of cells and spheroplasts of strains of LT2 and SL3600 resulted in hydrolysis of ATP. The outer membrane of gram-negative bacteria protects the cytoplasmic membrane from the action of brochocin-C. It appears that brochocin-C is similar to nisin and possibly does not require a membrane receptor for its function; however, the difference in effect of the two bacteriocins on intracellular ATP indicates that they cause different pore sizes in the cytoplasmic membrane.
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PMID:The outer membrane of gram-negative bacteria inhibits antibacterial activity of brochocin-C. 1050 55

The effects of maitotoxin (MTX) on plasmalemma permeability are similar to those caused by stimulation of P2Z/P2X(7) ionotropic receptors, suggesting that 1) MTX directly activates P2Z/P2X(7) receptors or 2) MTX and P2Z/P2X(7) receptor stimulation activate a common cytolytic pore. To distinguish between these two possibilities, the effect of MTX was examined in 1) THP-1 monocytic cells before and after treatment with lipopolysaccharide and interferon-gamma, a maneuver known to upregulate P2Z/P2X(7) receptor, 2) wild-type HEK cells and HEK cells stably expressing the P2Z/P2X(7) receptor, and 3) BW5147.3 lymphoma cells, a cell line that expresses functional P2Z/P2X(7) channels that are poorly linked to pore formation. In control THP-1 monocytes, addition of MTX produced a biphasic increase in the cytosolic free Ca(2+) concentration ([Ca(2+)](i)); the initial increase reflects MTX-induced Ca(2+) influx, whereas the second phase correlates in time with the appearance of large pores and the uptake of ethidium. MTX produced comparable increases in [Ca(2+)](i) and ethidium uptake in THP-1 monocytes overexpressing the P2Z/P2X(7) receptor. In both wild-type HEK and HEK cells stably expressing the P2Z/P2X(7) receptor, MTX-induced increases in [Ca(2+)](i) and ethidium uptake were virtually identical. The response of BW5147.3 cells to concentrations of MTX that produced large increases in [Ca(2+)](i) had no effect on ethidium uptake. In both THP-1 and HEK cells, MTX- and Bz-ATP-induced pores activate with similar kinetics and exhibit similar size exclusion. Last, MTX-induced pore formation, but not channel activation, is greatly attenuated by reducing the temperature to 22 degrees C, a characteristic shared by the P2Z/P2X(7)-induced pore. Together, the results demonstrate that, although MTX activates channels that are distinct from those activated by P2Z/P2X(7) receptor stimulation, the cytolytic/oncotic pores activated by MTX- and Bz-ATP are indistinguishable.
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PMID:Maitotoxin and P2Z/P2X(7) purinergic receptor stimulation activate a common cytolytic pore. 1051 7

Murine P388D(1) macrophages exhibit a delayed prostaglandin biosynthetic response when exposed to bacterial lipopolysaccharide (LPS) for prolonged periods of time that is dependent on induction of the genes coding for Group V secretory phospholipase A(2) and cyclooxygenase-2. We herein report that LPS-induced arachidonic acid (AA) metabolite release in P388D(1) macrophages is strongly attenuated by the P2X(7) purinergic receptor antagonists periodate-oxidized ATP and pyridoxal-phosphate-6-azophenyl-2', 4'-disulfonic acid, and this is accompanied by suppression of the expression of both Group V secretory phospholipase A(2) and cyclooxygenase-2. The effect appears to be specific for LPS, because the P2 purinergic receptor antagonists do not affect P388D(1) cell stimulation by other stimuli such as platelet-activating factor or the Ca(2+) ionophore A23187. Moreover, extracellular nucleotides are found to stimulate macrophage AA mobilization with a pharmacological profile that implicates the participation of the P2X(7) receptor and that is inhibited by periodate-oxidized ATP. Collectively these results demonstrate coupling of the P2X(7) receptor to the AA cascade in P388D(1) macrophages and implicate the participation of this type of receptor in LPS-induced AA mobilization.
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PMID:Regulation of arachidonic acid mobilization in lipopolysaccharide-activated P388D(1) macrophages by adenosine triphosphate. 1059 84

Salmonella typhimurium is a gram-negative bacterium that survives and replicates inside vacuolar compartments of macrophages. Infection of macrophages with S. typhimurium grown under conditions allowing expression of the type III secretion system results in apoptotic death of the infected cells. Here, we show that infection of bone marrow-derived macrophages (MPhi) with wild-type S. typhimurium 14028 results in presentation of epitopes derived from a bacteria-encoded antigen on major histocompatibility complex (MHC) class I and MHC class II molecules after internalization of apoptotic MPhi by bystander dendritic cells (DCs). In contrast, infection of MPhi with the phoP constitutive mutant strain CS022, which does not induce apoptosis in infected MPhi, does not result in presentation of a bacteria-derived antigen by bystander DCs unless the infected MPhi are induced to undergo apoptosis by treatment with lipopolysaccharide and ATP. DCs appear to be unique in their ability to present antigens derived from MPhi induced to undergo apoptosis by Salmonella, as bystander MPhi are not capable of presenting the bacteria-derived antigen despite the fact that they efficiently internalize the apoptotic cells. These data suggest that apoptosis induction by bacterial infection of MPhi may not be a quiescent death that allows the bacteria to escape recognition by the immune system, but rather may contribute to an antimicrobial immune response upon engulfment by bystander DCs.
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PMID:Salmonella-induced apoptosis of infected macrophages results in presentation of a bacteria-encoded antigen after uptake by bystander dendritic cells. 1068 53

Immune cell activation releases ATP into the extracellular space. ATP-sensitive P2 purinergic receptors are expressed on immune cells and activation of these receptors alters immune cell function. Furthermore, ATP is metabolized by ectonucleotidases to adenosine, which has also been shown to alter cytokine production. In the present study, we investigated how extracellular ATP affects interleukin (IL)-12 and tumour necrosis factor (TNF)-alpha production in bacterial lipopolysaccharide (LPS)-treated murine peritoneal macrophages and we also examined whether extracellular ATP alters the production of the T helper 1 cytokine interferon (IFN)-gamma. Pretreatment of the peritoneal macrophages with ATP or various ATP analogues decreased both IL-12 and TNF-alpha production induced by LPS (10 microgram ml(-1)). The effect of ATP was partially reversed by cotreatment with adenosine deaminase (0.1 - 1 u ml(-1)), suggesting that the suppressive effect of ATP on cytokine production is, in part, due to its degradation products. Immunoneutralization with an anti-IL-10 antibody demonstrated that although ATP increases IL-10 production, the inhibition of IL-12 and TNF-alpha production is independent of the increased IL-10. The effect of ATP was pretranslational, as it suppressed steady state levels of mRNAs for IL-12 (both p35 and p40). In spleen cells stimulated with either LPS (10 microgram ml(-1)) or anti-CD3 (2 microgram ml(-1)) antibody, ATP suppressed, in a concentration-dependent manner, the production of IFN-gamma. These results suggest that extracellular ATP has multiple anti-inflammatory effects and that release of ATP into the extracellular space may play a role in blunting the overactive immune response in autoimmune diseases.
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PMID:ATP suppression of interleukin-12 and tumour necrosis factor-alpha release from macrophages. 1069 89

Isolated human PMNs served as a model to determine oxyhemoglobin (oxyHb) binding and the effects of oxymyoglobin (oxyMb) or oxyHb on production of both nitric oxide (NO*) and superoxide (O2*-) and the resulting cytotoxicity. Physiologically relevant concentrations of NO* and H2O2 oxidized, to a similar extent, 2,7-dichlorodihydrofluorescein (DCFH) loaded into polymorphonuclear neutrophils (PMNs). Activation of PMNs with phorbol 12-myristate 13-acetate (PMA) markedly increased the internalization of extracellular oxyHb (10-250 microg/mL). OxyMb (10-300 microg/mL) or oxyHb (30-300 microg/mL) enhanced DCFH oxidation by a concentration-dependent mechanism in unstimulated, lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-alpha)-, and PMA-stimulated PMNs. This increased DCFH oxidation was eliminated by NO* synthase inhibitors, glutathione and ascorbate, and was reduced by albumin. Nitrite accumulation in PMN filtrates mirrored NO*-induced DCF fluorescence. OxyMb-induced increases in NO* levels paralleled alterations in DNA and cell membrane damage and ATP levels in PMNs and co-cultured lymphocytes, and were attenuated by NO* synthase inhibitors. OxyMb eliminated extracellular O2*- at protein concentrations 100- to 1000-fold above those of superoxide dismutase. These results suggest that heme proteins bind and internalize into PMNs and increase NO*-induced damage in neighboring cells by inhibiting O2*(-)-scavenging of NO*. We propose a mechanism whereby heme protein-induced NO* levels may contribute to immunosuppression and increased infection rates associated with transfusions and cellular damage during inflammation.
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PMID:Effects of heme proteins on nitric oxide levels and cell viability in isolated PMNs: a mechanism of toxicity. 1073 96

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