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)

In view of the accumulating evidence for paracrine mechanisms regulating trophoblast function, we tested the hypothesis that placental macrophages affect trophoblast activity in a paracrine fashion. Trophoblast was isolated from 17 term placentas (-IP). One aliquot of cells was further immunopurified (+IP) using an HLA class I antibody. This increased the proportion of trophoblast (+IP >97%; -IP approximately 70%) as identified by rigorous immunocytochemistry. Most (approximately 70%) non-trophoblast cells in -IP were macrophages. The cells were cultured for 5 days with a daily medium change. In addition, +IP cells from seven placentas were cultured with lipopolysaccharide (LPS)-stimulated or -unstimulated macrophage-conditioned media. The concentrations of lactate, trophoblast-specific hormones, human chorionic gonadotropin-beta (hCG-beta) and human placental lactogen (hPL), of several prostanoids and of endothelin-1 and angiotensin II were determined in the culture media. The accumulated amounts of substances released into the culture media, corrected for the greater proportion of trophoblast in +IP cultures, were on average two- to threefold higher (hCG-beta: 18-fold) in +IP than in -IP, with the exception of endothelin-1,2 (no change), angiotensin II (-70%) and 6-keto-prostaglandin-F1alpha (-40%). [3H]leucine incorporation into the trichloroacetic acid (TCA)-precipitable pool measured on day 5 was twofold higher in +IP than in -IP. Addition of conditioned media reverted these changes. The data demonstrate that placental macrophages in culture affect trophoblast biosynthetic activity in a paracrine fashion. We conclude that macrophages are important regulators of trophoblast activity.
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PMID:Paracrine regulation of distinct trophoblast functions in vitro by placental macrophages. 993 76

Oxidative stress and inflammatory reactions associated with stresses that may lead to shock promote hepatic microcirculatory dysfunction, which may lead to hepatic injury. Because altered liver microcirculation may result from an imbalance in the expression of stress-induced vasoactive mediators, our study was conducted to investigate changes in the expression of genes encoding endothelin-1 (ET-1), its receptors, ET(A) and ET(B), heme-oxygenase 1 (HO-1), and inducible nitric oxide synthase (iNOS), using two different rat models of liver stress: ischemia/reperfusion of the liver and lipopolysaccharide (LPS)-induced endotoxemia. In ischemia/reperfusion experiments, rats were subjected to 1 h hepatic ischemia, followed by 6 h of reperfusion. Endotoxemia was induced by i.p. injection of LPS (1 mg/mL/kg body weight); rats were studied after 6 h. mRNA levels were estimated using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on total RNA samples prepared from experimental and sham control rat livers. In the ischemic reperfused livers the levels of mRNA for ET-1, ET(B), HO-1, and iNOS were significantly elevated. The fold increase versus sham was 2.5+/-1.1 (ET-1), 2.1+/-1.3 (ET(B)), 2.1+/-.8 (HO-1), and 6.4+/-3.9 (iNOS). In contrast, the expression of ET(A) receptor gene was reduced after ischemia/reperfusion (to 73+/-1% of sham). In the separate experiments we analyzed the same mRNAs levels after 1 h of ischemia (no reperfusion), and did not detect any changes. During endotoxemia we observed a marked increase in iNOS mRNA level (>24-fold), as well as a marked elevation of the other four mRNAs. The fold increase versus sham was 6.1+/-1.7, ET-1); 1.5+/-.3 (ET(A)); 1.6+/-.4 (ET(B)); and 2.4+/-.34 (HO-1). These results show that liver stress, induced by ischemia/reperfusion or LPS injection have characteristic patterns of vasoregulatory genes expression indicating that, although both stresses result in an increase in specific vascular reactivity, different pathways are involved in inducing the hepatic vascular stress response.
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PMID:Patterns of vasoregulatory gene expression in the liver response to ischemia/reperfusion and endotoxemia. 1018 69

In this study, we investigated gastric mucosal inflammatory responses during Helicobacter pylori lipopolysaccharide-induced gastritis by analyzing the interplay between mucosal expression of endothelin-1 (ET-1), interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-alpha). The assays conducted 4 days after intragastric dose of H. pylori lipopolysaccharide demonstrated a pattern of acute mucosal reaction characterized by the inflammatory infiltration of the lamina propria, hyperemia, and epithelial hemorrhage. This was accompanied by a 3.1-fold increase in the mucosal expression of ET-1 and a 9-fold enhancement in TNF-alpha, while the level of IL-4 showed a 20.8% decline. The results implicate ET-1 in gastric mucosal responses to H. pylori, and suggest that an increase in its level, combined with a loss of compensatory action by IL-4, may be responsible for the induction of TNF-alpha and triggering apoptotic events that exacerbate the inflammatory process.
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PMID:Involvement of endothelin-1 in up-regulation of gastric mucosal inflammatory responses to Helicobacter pylori lipopolysaccharide. 1022 27

1. The potent coronary vasoconstrictor, endothelin-1 (ET-1) may also regulate neutrophil traffic into tissues. The aim of the present study was to characterize the endothelin receptors responsible and to investigate the underlying mechanisms. 2. ET-1 (1 nM - 1 microM) markedly enhanced attachment of human neutrophils to lipopolysaccharide-, and to a lesser extent, to ET-1-activated human coronary artery endothelial cells (HCAEC). This can partially be blocked by monoclonal antibodies against E-selectin, L-selectin or CD18, whereas combination of the three antibodies inhibited adhesion by approximately 83%. Increases in neutrophil adhesion evoked by ET-1 were also blocked by the platelet-activating factor (PAF) antagonists, BN 52021 (50 microM) and WEB 2086 (10 microM). 3. ET-1 downregulated the expression of L-selectin and upregulated expression of CD11b/CD18 and CD45 on the neutrophil surface and induced gelatinase release with EC50 values of approximately 2 nM. These actions of ET-1 were almost completely prevented by the ET(A) receptor antagonist FR 139317 (1 microM) and the ET(A)/ET(B) receptor antagonist bosentan (10 microM), whereas the ET(B) receptor antagonist BQ 788 (1 microM) had no effect. ET-1 slightly increased the expression of E-selectin and ICAM-1 on HCAEC, that was prevented by BQ 788, but not by FR 139317. 4. Receptor binding studies indicated the presence of ET(B) receptors (KD: 40 pM) on phosphoramidon-treated HCAEC and the predominant expression of ET(A) receptors (KD: 38 pM) on neutrophils. 5. These results indicate that promotion by ET-1 of neutrophil adhesion to HCAEC is predominantly mediated through activation of ET(A) receptors on neutrophils and subsequent generation of PAF.
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PMID:Endothelin-1 enhances neutrophil adhesion to human coronary artery endothelial cells: role of ET(A) receptors and platelet-activating factor. 1043 5

We investigated the modulation by endothelin-1 of lipopolysaccharide-induced cyclooxygenase 2 expression and prostaglandin E2 production by mouse peritoneal macrophages. Our previous report showed that endothelin-1 at concentrations above 10(-11) M induced cyclooxygenase 2 expression through mainly endothelin ET(B) receptors and that an endothelin ET(B) receptor-mediated process was not involved in cyclooxygenase 2 activation in macrophages stimulated by lipopolysaccharide for 4 h. In the present study, when macrophages were stimulated by lipopolysaccharide for 12 h in the presence of endothelin-1 (10(-15) to 10(-8) M), cyclooxygenase 2 expression and prostaglandin E2 production were enhanced by 1.2- to 1.6-fold. The endothelin ET(B) receptor selective antagonist, BQ788 (N-cis-2,6-dimethylpiperidino-carbonyl-L-gamma-methyl-leucyl-D-L-m ethoxycarbonyl-tryptophanyl-norleucine), significantly inhibited this synergistic effect of endothelin-1. In addition, the cyclooxygenase 2-selective inhibitor, NS398 (N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide), also suppressed this effect. Western blot analysis showed that the endothelin ET(B) receptor was up-regulated by lipopolysaccharide in a time- and concentration-dependent manner, and that this up-regulation was inhibited by NS398. From these results, we conclude that endothelin-1 promotes lipopolysaccharide-induced cyclooxygenase 2 activation in the delayed phase through endothelin ET(B) receptors up-regulated by lipopolysaccharide.
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PMID:Modulation by endothelin-1 of lipopolysaccharide-induced cyclooxygenase 2 expression in mouse peritoneal macrophages. 1044 89

We demonstrated previously that endothelin-1 (10(-14) to 10(-8) M) promotes lipopolysaccharide-induced cyclooxygenase 2 expression and prostaglandin E(2) production through endothelin ET(B) receptors effects which are up-regulated by lipopolysaccharide. In the present study, we confirmed these findings and showed that prostaglandin E(2) (10(-6) to 10(-5) M) inhibited the lipopolysaccharide plus endothelin-1-induced cyclooxygenase 2 expression more profoundly as compared to its inhibition of the lipopolysaccharide-induced cyclooxygenase 2 expression. The endothelin ET(B) receptor selective antagonist, N-cis-2, 6-dimethylpiperidino-carbonyl-L-gamma-methyl-leucyl-D-L-methoxy carbon yl-tryptophanyl-D-norleucine (BQ788), partly inhibited this suppression. Interestingly, the expression of endothelin ET(B) receptors in macrophages was increased by lipopolysaccharide plus prostaglandin E(2) (10(-8) to 10(-5) M) about 1.6-fold compared with that evoked by lipopolysaccharide stimulation alone. We also showed that treatment with endothelin-1 at 10(-14) M (15 min) elevated an intracellular cyclic AMP concentration in macrophages stimulated by lipopolysaccharide or lipopolysaccharide plus prostaglandin E(2) (10(-6) M) for 6 h, and the elevation in the latter cells was more pronounced. These results suggested that endothelin-1 shows an opposite modulation of lipopolysaccharide-induced cyclooxygenase 2 expression in macrophages through endothelin ET(B) receptors, depending on the level of extracellular prostaglandin E(2), and the changes of intracellular cyclic AMP by endothelin-1 may be involved in this mechanism.
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PMID:The effect of endothelin-1 on lipopolysaccharide-induced cyclooxygenase 2 expression in association with prostaglandin E(2). 1066 12

The endothelin-1 (ET-1) concentrations were measured by RIA in the media of confluent monolayer cultures of rat articular chondrocyte (RAC) exposed to fetal calf serum (FCS) and several growth factors and cytokines. The cells were obtained from 1- and 18-month-old rats. First passage cells were starved in Dulbecco's modified Eagle's medium (DMEM) containing 0.2% FCS serum for 24 h and then incubated for 48 h in the same fresh medium with each of the following factors: fetal calf serum (FCS), transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), lipopolysaccharide (LPS), and NO donor, sodium nitroprusside (SNP). The following was found: the cells from 18-month-old animals accumulated about twice as much ET-1 per microg DNA under basal (low serum) and stimulated conditions as cells from young rats. All, but PDGF and SNP produced concentration-dependent rise in ET-1 levels, the most effective being 10% FCS, IL-1beta, TNF-alpha, EGF, IGF-1 and LPS. TGF-beta caused the smallest stimulation and PDGF was ineffective or slightly inhibitory at high concentrations. SNP caused concentration-dependent decrease of ET-1 concentrations. ET-1-specific mRNA was identified by RT-PCR in cells incubated with the above factors and its concentration paralleled that of the peptide. This suggests that ET-1 found in the culture media of RAC stems, at least in part, from the synthesis. Increased immunoreactive peptide concentration and mRNA expression with the age of the donor rat and its regulation by several growth factors and cytokines suggest the involvement of ET-1 in chondrocytes' physiology and possibly pathology.
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PMID:Endothelin-1 in monolayer cultures of articular chondrocytes from young and old rats: regulation by growth factors and cytokines. 1073 80

Endothelin-1 (ET-1) is a strong bronchoconstrictor which possesses pro-inflammatory properties and is claimed to be an important mediator in bronchial asthma. The present study was undertaken to investigate whether ET-1 synthesis, in an inflammation dominated by neutrophilic granulocytes, is as pronounced as previously demonstrated in an airway inflammation dominated by eosinophils. Moreover, the authors compared the production of ET-1 and tumour necrosis factor (TNF)-alpha in rat lungs following intratracheal instillation of either lipopolysaccharide (LPS) (neutrophilic inflammation) or Sephadex (SDX) (eosinophilic). The lung tissue ET-1 messenger ribonucleic acid (mRNA) expression was not increased in LPS treated animals whereas a six-fold increase was measured after 30 min in the SDX group (p<0.05). TNF-alpha mRNA signals increased early following LPS instillation, peaking at 2 h, whereas elevated TNF-alpha mRNA in the SDX model was observed at 24 h. The ET-1 concentrations in bronchoalveolar lavage fluid (BALF) rose slightly, but significantly, 3 h after both LPS and SDX exposure. At 24 h no further rise in ET-1 levels was observed in the LPS model, while a substantial increase in the ET-1 concentration was measured in the SDX group (p<0.05). The TNF-alpha concentrations in BALF rose considerably at 3 h in the LPS group, but was nearly abolished at 24 h. In SDX challenged animals however, an increase in BALF-TNF-alpha did not occur until 24 h postchallenge. In conclusion, intratracheal instillation of lipopolysaccharide, leading to a purely neutrophilic lung inflammation, does not induce synthesis of endothelin-1. This is in contrast to observations during an eosinophilic airway inflammation, indicating a specific role of endothelin-1 in lung inflammations dominated by eosinophils. In contrast to in vitro experiments, no evidence for induction of endothelin-1 synthesis was observed by high levels of tumour necrosis factor-alpha in vivo.
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PMID:Endothelin-1 production is associated with eosinophilic rather than neutrophilic airway inflammation. 1078 Jul 68

1. The contractile effects of endothelin-1, isoprenaline and extracellular calcium were assessed on ventricular cardiomyocytes isolated from lipopolysaccharide-treated rats. The involvement of nitric oxide was investigated using dexamethasone (in vivo) and ethyl isothiourea (in vitro). 2. Male Wistar rats (n=70) were injected with either saline (1 ml kg(-1)) or lipopolysaccharide (LPS; 5 mg kg(-1)) alone, or following pre-treatment with dexamethasone (DEX+LPS; 5 mg kg(-1)). Ventricular cell shortening was recorded using a video edge detection system, and concentration-response relationships were established for endothelin-1, isoprenaline and calcium, in the absence or presence of ethyl isothiourea (ETU; 10 microM). iNOS expression was assessed using reverse transcription-polymerase chain reaction. 3. iNOS mRNA expression was greater (P<0.001) in the LPS (iNOS/GAPDH ratio: 0.90+/-0.09) treated group compared to saline (iNOS/GAPDH ratio: 0.36+/-0.02). Baseline contractile amplitude was reduced (P<0.05) in the LPS (7.3+/-0.2 microm) and DEX+LPS groups (6.7+/-0.3 microm) compared to saline (8. 0+/-0.2 microm). 4. The concentration-dependent contractile response to endothelin-1 was attenuated (P<0.05) in the LPS group compared to saline (maximum change: 0.45+/-0.2 vs 1.8+/-0.2 microm). Neither ETU nor dexamethasone improved contractile function in the LPS-treated animals. 5. The concentration-dependent increase in the contractile response to isoprenaline was attenuated in the LPS-treated group compared to saline (P<0.05; maximum change: 1.7+/-0.4 vs 3.1+/-0.4 microm). This effect was reversed by ETU (maximum change: 3.7+/-0.6 microm). Pre-treatment with dexamethasone prevented a significant fall in contraction amplitude (maximum change: 2.4+/-0.4 microm). 6. The contractile response to calcium was reduced (P<0.05) in the LPS group compared to saline (maximum change: 8.7+/-0.6 vs 10.7+/-0.8 microm). Neither ETU nor dexamethasone restored contractile function in the LPS-treated group. 7. In conclusion, a nitric oxide-mediated inhibitory pathway is not responsible for the diminished contractile response to either endothelin-1 or extracellular calcium, but contributes to the hyporesponsiveness to isoprenaline in lipopolysaccharide treated rats.
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PMID:Inotropic response to endothelin-1, isoprenaline and calcium in cardiomyocytes isolated from endotoxin treated rats: effects of ethyl-isothiourea and dexamethasone. 1090 66

Bacterial lipopolysaccharide (LPS) was found to induce inflammatory responses and to enhance bronchial hyperreactivity to several contractile agonists. However, the implication of LPS in the pathogenesis of bronchial hyperreactivity was not completely understood. Therefore, in this study, we investigated the effect of LPS on mitogen-activated protein kinase (MAPK) activation associated with potentiation of bradykinin (BK)-induced inositol phosphates (IPs) accumulation and Ca(2+) mobilization in canine cultured tracheal smooth muscle cells (TSMCs). LPS stimulated phosphorylation of p42/p44 MAPK in a time- and concentration-dependent manner using a Western blot analysis against a specific phosphorylated form of MAPK antibody. Maximal stimulation of the p42 and p44 MAPK isoforms occurred after 7 min-incubation and the maximal effect was achieved with 100 microg ml(-1) LPS. Pretreatment of TSMCs with LPS potentiated BK-induced IPs accumulation and Ca(2+) mobilization. However, there was no effect on the IPs response induced by endothelin-1, 5-hydroxytryptamine, and carbachol. In addition, pretreatment with PDGF-BB enhanced BK-induced IPs response. These enhancements by LPS and PDGF-BB might be due to an increase in BK B(2) receptor density (B(max)) in TSMCs, characterized by competitive inhibition of [(3)H]-BK binding using B(1) and B(2) receptor-selective reagents. The enhancing effects of LPS and PDGF-BB were attenuated by PD98059, an inhibitor of MAPK kinase (MEK), suggesting that the effect of LPS may share a common signalling pathway with PDGF-BB in TSMCs. Furthermore, overexpression of dominant negative mutants, H-Ras-15A and Raf-N4, significantly suppressed p42/p44 MAPK activation induced by LPS and PDGF-BB, indicating that Ras and Raf may be required for activation of these kinases. These results suggest that the augmentation of BK-induced responses produced by LPS might be, at least in part, mediated through activation of Ras/Raf/MEK/MAPK pathway in TSMCs.
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PMID:Lipopolysaccharide enhances bradykinin-induced signal transduction via activation of Ras/Raf/MEK/MAPK in canine tracheal smooth muscle cells. 1095 68


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