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)

Intracellular enterocytic levels of the immunomodulator taurine decrease significantly in response to trauma and surgical insult. The effect of physiological stress on enterocyte taurine uptake is unknown. The aim of this study was to compare taurine transport under basal and stressed conditions using the human intestinal Caco-2 cell line in vitro. Caco-2 cells were incubated with 10 nM [1,2-3H]taurine at 37 degrees C and 5% CO2 and taurine uptake was examined over the range of 0.1-10 microM to determine kinetic parameters of the transporter. The culture medium was then supplemented with dexamethasone and/or lipopolysaccharide (LPS) and taurine uptake was calculated as picomoles per milligram protein per hour. Statistics were by unpaired Student's t test. Taurine uptake was hyperbolically related to taurine concentration and obeyed Michaelis-Menten kinetics with a K(m) of 5.27 +/- 0.95 microM and Vmax of 1125.43 +/- 130.9 pmole/mg protein/ hour. Dexamethasone (1-1000 microM) significantly reduced taurine uptake by up to 66.15%. LPS (1 microgram/ml) impaired transport of taurine by 15.7%, and in combination with dexamethasone (100 microM) by 42.4%. All results are mean of at least three experiments and P < 0.05. We have established that taurine uptake by enterocytes is downregulated by dexamethasone. This may relate to the decreased intestinal levels of taurine observed in trauma and surgery patients. Further study may elucidate mechanisms whereby homeostasis of enterocyte taurine might be maintained during sepsis.
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PMID:Dexamethasone and lipopolysaccharide regulation of taurine transport in Caco-2 cells. 922 2

Tumor necrosis factor (TNF) is involved in the pathogenesis of acute sepsis-induced organ injury and has been implicated as a mediator of metabolic alterations observed during sepsis. Pancreatic islet cell function may be significantly compromised during sepsis or endotoxemia, and sepsis also increases plasma levels of epinephrine, a modifier of islet insulin secretion. We proposed that islets exposed to bacterial lipopolysaccharide (LPS) produce TNF and that epinephrine attenuates islet secretory activity. We monitored the effects of LPS and epinephrine on TNF and insulin activity of isolated Wistar-Furth rat islets (pancreas digested with collagenase, islets isolated using Ficoll gradients; n = 4 islet populations, each with 632 +/- 11 islets/2.5 ml culture medium). Islets were incubated (37 degrees C, 5% CO2) 3 days. LPS (Escherichia coli, 1 microgram/ml) and epinephrine (14 micrograms/ml) were added to the islets, and incubations were continued for 1-4 h. Glucose (Beckman Glucose Analyzer), insulin (radioimmunoassay), and TNF (L929 cytotoxicity assay) were measured in the islet medium samples at 1- to 4-h time points. In the conditioned medium, glucose decreased (P < 0.05), insulin increased (P < 0.05), and exposure to LPS did not alter these levels [P = not significant (NS)] but did increase TNF activity by 400% (P < 0.05). Epinephrine reduced insulin by 38-43% (P < 0.05) and TNF by 20-25% (P < 0.05) but had no effect on glucose levels (P = NS). We conclude that insulin is secreted from isolated islets and that exposure to LPS acutely increases islet-derived TNF activity, whereas epinephrine modifies TNF and insulin secretion of rat pancreatic islets.
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PMID:Tumor necrosis factor activity of pancreatic islets. 927 98

Actinobacillus actinomycetemcomitans(Aa), elaborating a multiplicity of virulence factor and tissue-damaging products, is considered an etiological agent in periodontal disease. Serotype b is the most frequently isolated serotype in localized juvenile periodontitis patients, suggesting a particularly high periodontopathic potential for serotype b strains. Interleukin-6(IL-6) plays an important role in the mediation of inflammatory and immune responses as well as in the osteoclastic bone resorption. However, there is little information regarding the effect of the different serotypes of Aa on IL-6 production by human gingival fibroblasts (HGF). Therefore, the purpose of this study was to compare the ability of the three serotypes (a, b, and c) of Aa sonicates to induce the production of IL-6 by HGF. In fibroblast cultures, confluent monolayers of HGF were incubated with sonic extracts of Aa-511 (serotype a), Aa-Y4 (serotype b), and Aa-652 (serotype c) at various concentrations for 48 h at 37 degrees C in 5% CO2 and air. At the end of the culture period, supernatants were collected and analysed for IL-6 content by using EIA and bioassay. In order to compare the effects of non-lipopolysaccharide (LPS) activation of Aa sonicates on IL-6 production by HGF, we added polymyxin B in cultures with Aa sonicates to bind LPS. The results were summarized as follows. (1) All three serotypes of Aa sonicates had similar dose-dependent stimulant effects on IL-6 production by HGF, and the biological activities of IL-6 correlated with their immunoreactivities. (2) The maximum releases of IL-6 by HGF were achieved at concentrations of 10 to 100 micrograms protein/mL of Aa sonicates, and the ability of Aa-Y4 to induce the release of IL-6 was higher than that of Aa-511 and Aa-652 at these concentrations. (3) Polymyxin B (50 micrograms/mL) effectively decreased the amounts of IL-6 produced by stimulation of the HGF with 10 micrograms protein/mL of Aa sonicates. However, the polymyxin B-treated Aa-Y4 sonicate showed a higher ability to induce the release of IL-6 than the other two strains. These results indicate that Aa-Y4 (serotype b) has a higher potency to induce HGF secretion of IL-6; thus contributing to a comparatively stronger efficacy to the destruction of periodontal tissue in periodontitis.
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PMID:[Interleukin-6 production by human gingival fibroblasts following stimulation with Actinobacillus actinomycetemcomitans]. 971 39

We previously showed that incubation in carbon dioxide (CO2), but not air or helium (He), markedly decreased macrophage intracellular pH (pHi) and resulted in reversible inhibition of lipopolysaccharide- (LPS) stimulated tumor necrosis factor (TNF) and interleukin-1 release. We sought to determine whether carbonic anhydrase inhibition with acetazolamide would prevent CO2-mediated inhibition of LPS-stimulated TNF release. Murine peritoneal macrophages were treated with acetazolamide for 1 h under control atmosphere (95% air/5% CO2) and then switched to incubator modules containing: 1) 80% CO2/20% O2, 2) 80% He/20% O2, or 3) 100% air. Before transfer to experimental atmospheric conditions the macrophages were stimulated with 0 or 1 microg/mL of LPS (Escherichia coli 0111 B4). Supernatant TNF was measured 4 h later by bioassay. In parallel experiments LPS-stimulated cytokine mRNA was estimated using reverse transcriptase polymerase chain reaction (RT-PCR) 2 h after LPS stimulation. Viability was determined using dye uptake. Incubation in CO2 or helium had no effect on TNF production in the absence of LPS. In the absence of acetazolamide CO2 produced marked inhibition of LPS-stimulated TNF release, but this was not blocked by the presence of acetazolamide. This CO2-mediated inhibition of TNF was associated with normal levels of TNF mRNA. In acetazolamide-treated macrophages, LPS resulted in a dose-dependent inhibition of TNF release when the cells were incubated in air or helium. Maintenance of normal intracellular pH is required for TNF release, but not TNF mRNA induction by LPS. Factors that alter intracellular pH regulation may modulate LPS-stimulated cytokine production.
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PMID:Acetazolamide treatment prevents in vitro endotoxin-stimulated tumor necrosis factor release in mouse macrophages. 987 84

Early systemic arterial hypotension is a common clinical feature of Pseudomonas septicemia. To determine if Pseudomonas aeruginosa endotoxin induces the release of endothelium-derived nitric oxide (EDNO), an endogenous nitrovasodilator, segments of canine femoral, renal, hepatic, superior mesenteric, and left circumflex coronary arteries were suspended in organ chambers (physiological salt solution, 95% O2/5% CO2, pH 7.4, 37 degrees C) to measure isometric force. In arterial segments contracted with 2 microM prostaglandin F2 alpha, Pseudomonas endotoxin (lipopolysaccharide (LPS) serotype 10(Habs) from Pseudomonas aeruginosa (0.05 to 0.50 mg/ml) induced concentration-dependent relaxation of segments with endothelium (P < 0.05) but no significant change in tension of arteries without endothelium. Endothelium-dependent relaxation in response to Pseudomonas LPS occurred in the presence of 1 microM indomethacin, but could be blocked in the coronary artery with 10 microM NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthesis from L-arginine. The inhibitory effect of L-NMMA on LPS-mediated vasorelaxation of the coronary artery could be reversed by exogenous 100 microM L-arginine but not by 100 microM D-arginine. These experiments indicate that Pseudomonas endotoxin induces synthesis of nitric oxide from L-arginine by the vascular endothelium. LPS-mediated production of EDNO by the endothelium, possibly through the action of constitutive nitric oxide synthase (NOSc), may decrease systemic vascular resistance and may be the mechanism of early hypotension characteristic of Pseudomonas septicemia.
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PMID:Endothelium-dependent vasodilation in response to Pseudomonas aeruginosa lipopolysaccharide: an in vitro study on canine arteries. 987 5

The role of calcium in transducing the signal for interleukin-1 (IL-1) secretion was examined in the MQ-NCSU chicken macrophage cell line. Cells were maintained in RPMI 1640 medium supplemented with 5% chicken serum and antibiotic-antimycotic solution at 40 C and 5% CO2. The effects of stimulation with lipopolysaccharide (LPS), calcium ionophore A23187, or a combination of both on IL-1 secretion were examined. Calcium ionophore A23187 did not replace LPS in MQ-NCSU stimulation but the LPS + A23187 combination stimulated more IL-1 than ionophore alone in these cells. The combination of LPS and ionophore did not increase IL-1 secretion above the levels observed with LPS alone. No synergistic effects between LPS and A23187 were evident. In order to demonstrate that IL-1 secretion by the MQ-NCSU cells is a calcium-dependent process, ethylene glycol bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA) was used to chelate free calcium in the cultures. Incorporation of 5 mM EGTA in the cultures lowered IL-1 stimulated by LPS + A23187 to control levels. Addition of 5 mM CaC12 to EGTA-suppressed cultures restored IL-1 secretion. These results indicate that the calcium ionophore, A23187, augments IL-1 secretion by LPS-stimulated MQ-NCSU macrophages and that IL-1 secretion by these cells is a calcium-dependent process.
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PMID:Calcium dependency of interleukin-1 secretion by a chicken macrophage cell line. 1002 50

Due to their peripheral location in the dental pulp and their cellular extension into dentin, odontoblasts are the first pulpal cells to encounter dental pathogens. The association of odontoblasts with immunoglobulins and dendritic cells during microbial invasion of dentin implies that these cells may possess a role in the innate and adaptive pulpal immune responses, however this has not been examined. A pivotal step in the innate immune response is the detection of foreign antigen and the recruitment of immune effector cells to the area. IL-8 is a potent chemotactic cytokine that plays an important role in the inflammatory response. The purpose of this study was to determine if odontoblasts are capable of expressing the pro-inflammatory chemokine IL-8. Human odontoblasts from intact, noncarious third molars were maintained in culture and exposed to Escherichia coli lipopolysaccharide (LPS) (serotype 055:B5) on day 4 for 8-10 h in a humidified 5% CO2 incubator. Control and experimental samples were assayed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot for the production of IL-8 mRNA and protein. Analysis of the PCR products revealed that cells of the odontoblast layer maintained in this culture model constitutively expressed low levels of IL-8, which were increased in response to E. coli LPS exposure. Western blotting confirmed that the mRNA was translated into protein. These results imply that odontoblasts are capable of producing of pro-inflammatory mediators, thereby actively participating in the recruitment of neutrophils in response to bacterial by-products.
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PMID:Expression of IL-8 by cells of the odontoblast layer in vitro. 1023 62

The prophylactic effects of selectin inhibitors on lipopolysaccharide-induced acute lung injury were studied in rabbits by using sialyl Lewis X-oligosaccharide and PB1.3, an anti-human P-selectin monoclonal antibody. Lipopolysaccharide-induced acute lung injury resembles that of the acute respiratory distress syndrome, in which there is a decrease in arterial blood oxygen tension (PaO2) and an increase in the difference between alveolar and arterial oxygen tension (A-aDO2). Prophylactic treatment with the selectin inhibitors, sialyl Lewis X-oligosaccharide (55 mg kg(-1) i.v. bolus injection immediately before lipopolysaccharide administration + 36 mg kg(-1) h(-1) i.v. infusion for 4 h) and PB1.3 (5 mg kg(-1) i.v. bolus injection immediately before lipopolysaccharide administration), prevented the lipopolysaccharide-induced impairments in pulmonary gas exchange. In contrast, these agents had no significant effects on lipopolysaccharide-induced systemic hypotension, the decrease in the number of circulating white blood cells and platelets, the decline in blood pH, or the increase in arterial CO2 tension (PaCO2). These results indicate that selectin inhibitors including sialyl Lewis X-oligosaccharide and the anti-P-selectin antibody, PB1.3, attenuate lipopolysaccharide-induced acute lung injury in rabbits. This is the first demonstration that P-selectin is directly involved in the development of lipopolysaccharide-induced impairments in pulmonary gas exchange.
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PMID:Protective effects of sialyl Lewis X and anti-P-selectin antibody against lipopolysaccharide-induced acute lung injury in rabbits. 1032 79

Alterations in alveolar macrophage (AM) function during sepsis-induced hypoxia may influence tumor necrosis factor (TNF) secretion and the progression of acute lung injury. Nuclear factor (NF)-kappaB is thought to regulate the expression of endotoxin [lipopolysaccharide (LPS)]-induced inflammatory cytokines such as TNF, and NF-kappaB may also be influenced by changes in O2 tension. It is thus proposed that acute changes in O2 tension surrounding AMs alter NF-kappaB activation and TNF secretion in these lung cells. AM-derived TNF secretion and NF-kappaB expression were determined after acute hypoxic exposure of isolated Sprague-Dawley rat AMs. Adhered AMs (10(6)/ml) were incubated (37 degrees C at 5% CO2) for 2 h with LPS (Pseudomonas aeruginosa, 1 microgram/ml) in normoxia (21% O2-5% CO2) or hypoxia (1.8% O2-5% CO2). AM-derived TNF activity was measured with a TNF-specific cytotoxicity assay. Electrophoretic mobility shift and supershift assays were used to determine NF-kappaB activation and to identify NF-kappaB isoforms in AM extracts. In addition, mRNAs for selected AM proteins were determined with RNase protection assays. LPS-exposed AMs in hypoxia had higher levels of TNF (P < 0.05) and enhanced expression of NF-kappaB (P < 0.05); the predominant isoforms were p65 and c-Rel. Increased mRNA bands for TNF-alpha, interleukin-1alpha, and interleukin-1beta were also observed in the hypoxic AMs. These results suggest that acute hypoxia in the lung may induce enhanced NF-kappaB activation in AMs, which may result in increased production and release of inflammatory cytokines such as TNF.
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PMID:Acute hypoxia increases alveolar macrophage tumor necrosis factor activity and alters NF-kappaB expression. 1036 14

This study was designed to investigate VEGF production from peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) compared with healthy controls and to identify the predominant cellular source in PBMC isolated from RA patients. The regulation of PBMC VEGF production by cytokines and synovial fluid (SF) was studied. PBMC were isolated from RA patients and healthy controls and stimulated with lipopolysaccharide (LPS), IL-1beta, IL-4, IL-6, IL-8, IL-10, TNF-alpha and transforming growth factor-beta (TGF-beta) isoforms for varying time points up to 72 h at 37 degrees C/5% CO2. The effect of SF on VEGF secretion by PBMC was also studied. Supernatant VEGF levels were measured using a flt-1 receptor capture ELISA. RA patients had significantly higher spontaneous production of VEGF compared with controls, and monocytes were identified as the predominant cellular source. RA PBMC VEGF production was up-regulated by TGF-beta isoforms and TNF-alpha and down-regulated by IL-4 and IL-10, with no effect observed with IL-1beta, IL-6 and IL-8. Antibody blocking experiments confirmed that TNF-alpha and not TGF-beta isoforms in SF increased VEGF secretion by RA PBMC. These results emphasize the importance of monocytes as a source of VEGF in the pathophysiology of RA. Several cytokines known to be present in SF can modulate the level of VEGF secretion, but the predominant effect of SF in VEGF up-regulation is shown to be dependent on TNF-alpha.
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PMID:Peripheral blood mononuclear cells from patients with rheumatoid arthritis spontaneously secrete vascular endothelial growth factor (VEGF): specific up-regulation by tumour necrosis factor-alpha (TNF-alpha) in synovial fluid. 1040 32


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