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)

Inducible nitric oxide synthase (iNOS) catalyzes the formation of nitric oxide (NO) from L-arginine and O2. Although some O2 is required for this reaction, it is uncertain whether biologically relevant levels of hypoxia alter this pathway. We examined the effects of graded hypoxia on several steps in the iNOS pathway in lipopolysaccharide (LPS)-stimulated rat glomerular mesangial cells: induction of iNOS mRNA, NO synthesis, NO oxidation to nitrite (NO2-) and nitrate (NO3-), and accumulation of cGMP. Cultured cells were incubated for 24 hours in airtight flasks containing O2 (21%, 10%, 2.5%, and 0%), CO2 (5%), and N2 (balance), resulting in media PO2 levels of 140 +/- 3, 85 +/- 1, 46 +/- 3 (moderate hypoxia), and 32 +/- 5 (severe hypoxia) mm Hg, respectively. During normoxia (PO2, 85 to 140 mm Hg) LPS increased iNOS mRNA with associated increases in NO synthesis, NO2- and NO3- accumulation, and intracellular cGMP levels. In the absence of LPS, there was minimal NO synthesis and no detectable iNOS mRNA. Even during severe hypoxia, LPS elevated NO2- and NO3- relative to levels in unstimulated cells (P < .05), although to a lesser extent than during normoxia (P < .05). The induction of iNOS mRNA by LPS was preserved in hypoxia, and intracellular cGMP levels were similar at all levels of oxygen tension, indicating that iNOS induction and function were not altered by moderate or severe hypoxia. However, moderate hypoxia did alter the partitioning and oxidation of NO, favoring the appearance of NO in the "headspace" (defined as the gas overlying the cells) and NO3- in the media.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of graded hypoxia on the induction and function of inducible nitric oxide synthase in rat mesangial cells. 754 May 15

Tissue injury that occurs as a result of ischemia and subsequent reperfusion is characterized by endothelial cell injury, edema formation, and the influx of inflammatory leukocytes. Two macrophage-derived proinflammatory cytokines which may play a critical role in cellular injury and leukocyte recruitment/activation that occurs in the setting of ischemia-reperfusion injury are tumor necrosis factor alpha (TNF) and macrophage inflammatory protein-1 alpha (MIP-1 alpha). To determine if modulation of ambient oxygen tensions in vitro alters the expression of proinflammatory cytokines from activated macrophages, murine alveolar macrophages (AMO) were cultured in various combinations of ambient oxygen concentrations, then the supernatant fluid and cell pellet assayed for the presence of TNF and MIP-1 alpha messenger RNA (mRNA) and protein. We demonstrated that conditions of anoxia (95% nitrogen/5% CO2) or hyperoxia (95% oxygen/5% CO2) independently resulted in the increased expression of both TNF and MIP-1 alpha mRNA and protein from lipopolysaccharide (LPS)-stimulated AMO, as compared with cells cultured in room air. The specific culture condition of anoxia (x 6 h) followed by hyperoxia (x 18 h) produced the greatest increases in both TNF and MIP-1 alpha, suggesting that when following a period of anoxic priming, oxygen stress results in exaggerated cytokine production. A period of at least 4.5 to 6 h of anoxia prior to hyperoxic exposure was found to be the minimal time required for anoxic priming. Furthermore, the coincubation of LPS-treated AMO with dimethyl sulfoxide (DMSO) attenuated the anoxia-hyperoxia-induced increases in TNF and MIP-1 alpha mRNA by 23% and 34%, respectively. These findings suggested that alterations in ambient oxygen tension can regulate the expression of TNF and MIP-1 alpha from activated AMO, and that oxidant-related cytokine production may represent an important mechanism by which inflammation occurs in the clinical settings of ischemia-reperfusion injury and hyperoxia.
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PMID:Alterations of ambient oxygen tension modulate the expression of tumor necrosis factor and macrophage inflammatory protein-1 alpha from murine alveolar macrophages. 754 69

Resident alveolar macrophages (m phi) possess plasmalemmal vacuolar-type H(+)-ATPase (V-ATPase) that plays a crucial role in regulation of intracellular pH (pHi). To assess the importance of this V-ATPase to m phi effector functions, resident alveolar m phi from rabbits were activated with E. coli-derived lipopolysaccharide (LPS) and exposed to bafilomycin A1, a specific inhibitor of V-ATPase. Bafilomycin caused a significant cytosolic acidification in both the absence and presence of CO2-HCO3-, and in both unstimulated and activated m phi. Superoxide production and Fc receptor-mediated phagocytosis also were reduced in bafilomycin-treated m phi. Similar effects were elicited by acidifying the cytoplasm in the absence of bafilomycin, by lowering extracellular pH (pHo) from 7.4 to 6.5-6.6. Thus, the effects of bafilomycin on phagocytosis and superoxide production probably were related to cytosolic acidification, secondary to blockade of V-ATPase-mediated H+ extrusion across the plasma membrane. Conversely, bafilomycin significantly increased TNF-alpha release. This effect cannot be explained by a bafilomycin-induced acidosis because acidic pHo significantly reduced TNF-alpha release. The results demonstrate that V-ATPase activity is an important determinant of the effector functions of LPS-activated m phi.
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PMID:Effects of bafilomycin A1 on functional capabilities of LPS-activated alveolar macrophages. 785 42

The mechanisms underlying the multiple biological activities presented by interleukin-3 (IL-3) are not yet fully understood. As a regulator of hematopoiesis, IL-3 is known to interact with several other molecules. The present study investigates the interaction of IL-3 and Escherichia coli lipopolysaccharide (LPS), which results in the inhibition of the in vitro proliferation of mouse bone marrow (BM) cells. BM cells from adult BALB/c mice were cultured at 37 degrees C, with 5% CO2 in air, in RPMI-1640 medium complemented with fetal calf serum. Viable cells were counted on day 3. Whereas IL-3 and LPS alone increased the number of viable cells as compared to control cultures, the simultaneous addition of the factors lowered that number below controls. Cell fractions of different densities, isolated by Percoll gradient (70, 50 and 40%), also behaved in the same way. The same effect was observed when BM non-adherent cells were isolated 1 day after initiation of cultures and analyzed 2 days later, but not if the culture was initiated in the absence of adherent cells. Pre-incubation experiments showed that only if total BM cells were pre-incubated for 24 h with IL-3/LPS or LPS alone was the inhibitory effect of the two factors maintained. Soluble inhibitory factors were only observed in cultures of adherent BM cells.
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PMID:Interleukin-3 and lipopolysaccharide interact to inhibit proliferation of mouse bone marrow cells. 792 14

In this study we evaluated the effect of cigarette smoke on the activation of alveolar macrophages of the rat lungs exposed to an episode of acute passive cigarette smoking. Our experiments were carried out in rats that, after undergoing smoking (3 cigarettes within 1 h) showed a COHb increase of about 16%. The evaluation of the kinetics of alveolar and peritoneal macrophages, indicated that the number of alveolar macrophages in the bronchoalveolar lavage fluids significantly increased 8 h after the smoking session, whereas the number of peritoneal macrophages remained practically constant. Alveolar macrophages collected 0.8 and 24 h after smoking and incubated for 24 h at 37 degrees C in an atmosphere of 5% CO2 in air spontaneously released 5 +/- 1, 48 +/- 14 and 15 +/- 9 units of TNF-alpha per 10(6) cells, respectively. Moreover, neither alveolar macrophages collected from smokers, nor those collected from controls, released IFN, and both cytokines were also absent either in bronchoalveolar lavage and peritoneal lavage fluids or in plasma. Alveolar macrophages collected from controls rats, when challenged with lipopolysaccharide (LPS), released more TNF than those collected from smoke exposed rats. Thus, it seemed that macrophages of experimental animals were activated but at the same time were somewhat depressed and responded less well to LPS.
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PMID:Production of tumor necrosis factor alpha by rat alveolar macrophages collected after acute cigarette smoking. 801 Aug 75

Interferon production in spotted sousliks in different physiological states: in summer activity, summer torpor, winter hibernation and awaked from winter hibernation was studied. Three different interferon inducers: poly rI:rC complexed with DEAE-dextran, lipopolysaccharide from E. coli (LPS) and tilorone hydrochloride were used. In comparison with sousliks active in summer, the interferon levels in serum and different organs of sousliks in winter hibernation after induction with tilorone hydrochloride, LPS and poly rI:rC were significantly lower. Decreased interferon response was also observed in sousliks in summer torpor and awaked from winter hibernation. In contrast to hibernation, artificial acidosis induced by placing sousliks in the atmosphere with a high concentration of CO2 enhanced interferon production.
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PMID:Seasonal modulation of interferon response in spotted sousliks (Spermophilus suslicus). 857 2

Our previous work demonstrated that hypoxia decreases transcription of the human prostaglandin H synthase-2 (PGHS-2) gene during exposure to lipopolysaccharide (LPS), resulting in decreased prostaglandin E2 (PGE2) synthesis (J. Biol. Chem. 269:32979-32984, 1994). Because PGE2 is reported to inhibit interleukin 1 (IL-1) and tumor necrosis factor (TNF), it is likely that hypoxia, through changes in PGE2, will alter IL-1 and TNF release from the human alveolar macrophage. In addition, like PGHS-2, the TNF and IL-1 promoters contain oxidant-sensitive elements which might be altered by hypoxia. Therefore, we hypothesized that LPS-induced release of TNF and IL-1 would be altered by hypoxia. To test this, human alveolar macrophages were cultured for 24 h with 0 to 1 microgram/ml LPS in a room-air incubator with 5% CO2 or a hypoxia incubator continuously perfused with 5% CO2/95% N2 (O2 < 0.05%). With room air, LPS increased IL-1 beta mRNA and increased IL-1 beta protein release into the culture medium in a dose-dependent manner. Hypoxia increased the LPS-stimulated release of IL-1 beta 30% above that of room-air controls. However, immunoblots showed that hypoxia caused no change in intracellular IL-1 beta compared with room-air controls. There was also no change in LPS-induced IL-1 beta message with hypoxia. The inhibitor of IL-1, IL-1RA, was apparently decreased by hypoxia, but this decrease was not statistically significant. TNF-alpha mRNA and release of protein also increased during LPS exposure in room air. Hypoxia markedly increased LPS-induced TNF-alpha message and release of TNF-alpha compared with LPS-exposed room-air controls. Consistent with our prior observations, hypoxia decreased LPS-induced PGHS-2 message and protein, and also the PGHS-2 product, PGE2. Because PGE2 is reported to inhibit the expression of IL-1 and TNF genes, we inhibited PGE2 synthesis with indomethacin during culture in room air; the result was an increase in the release of IL-1 and TNF. In additional studies, adding PGE2 inhibited TNF release from the hypoxia cells to values near those of room-air controls. In summary, hypoxia increases the release of the cytokines IL-1 beta and TNF-alpha. This increase may be due to decreased PGE2 synthesis during hypoxia. These results demonstrate that the response of the human alveolar macrophage to hypoxia is complex. Hypoxia increases the LPS-stimulated release of the inflammatory cytokines IL-1 and TNF, whereas synthesis of PGHS-2, which generates the anti-inflammatory prostaglandin PGE2 is decreased.
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PMID:Effect of hypoxia on release of IL-1 and TNF by human alveolar macrophages. 863 Feb 67

The mechanisms responsible for the lack of inflammation after laparoscopic surgery remain unknown. Peritoneal macrophages (M phi) incubated in carbon dioxide (CO2) but not air or helium (He), had significant, reversible inhibition of lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) and interleukin-1 (IL-1) release. In these experiments the kinetics of these C02-induced alterations in cytokine secretion were examined. Murine peritoneal Mphi were stimulated with LPS for 4 hr and incubated in different test gases (95% air/5% CO2,80%CO2/20%O2,80% He/20% O2) for intervals between 0.25 and 4 hr. Time between gas incubation and LPS stimulation was varied to determine the persistence of CO2 inhibition. Parallel M phi groups received LPS stimulation 24 hr later. Supernatant TNF and IL-1 were measured by bioassay and polymerase chain reaction was used to examine cytokine mRNA. Significant reversible inhibition of TNF and IL-1 was seen with CO2, but not He or air. Inhibition of IL-1 occurred 15 min after CO2 exposure, was associated with decreased IL-1 mRNA, and was rapidly lost following incubation in the control atmosphere. TNF inhibition was seen despite normal levels of TNF message, required more than 30 min of CO2 exposure, and persisted after CO2 removal. CO2 produced profound, reversible, inhibition of LPS-stimulated cytokine release by peritoneal Mphi. The transient inability to secrete inflammatory cytokines after CO2 exposure may explain the lack of systemic inflammation after laparoscopic surgery with CO2.
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PMID:Kinetics of decreased LPS-stimulated cytokine release by macrophages exposed to CO2. 866 Dec 9

The role of individual cell types in hepatic hypoxia-reoxygenation (reperfusion) injury has not been completely defined. We therefore examined the effects of hypoxia and hypoxia-reoxygenation on the viability of rat hepatocytes, Kupffer cells, and sinusoidal endothelial cells (SECs) in primary culture and whether direct exposure to hypoxia followed by reoxygenation activated Kupffer cells. Cultures of hepatocytes (purity > 99%), Kupffer cells (97%), and endothelial cells (> 93%) were established as single-cell types and as cocultures. Hypoxia was achieved by culturing cells under 95% N2/5% CO2, and cell viability was estimated by lactate dehydrogenase (LDH) leakage and Trypan blue exclusion. Kupffer cells and endothelial cells were more resistant to hypoxia than hepatocytes. Following 4-8 hours of hypoxia, reoxygenation accentuated cell death in endothelial cells. In contrast, reoxygenation did not accentuate cell death in hepatocytes or in resting Kupffer cells. The activation of Kupffer cells by the addition of lipopolysaccharide failed to alter their response to hypoxia-reoxygenation. The addition of phorbol myristate acetate to Kupffer cells stimulated the production of superoxide as expected, and the medium from these activated cells augmented the cellular injury of hypoxic hepatocytes. In contrast, hypoxia-reoxygenation did not stimulate Kupffer cells to produce superoxide or other hepatotoxic products. Moreover, Kupffer cells in coculture with hepatocytes did not augment hepatocyte injury after hypoxia-reoxygenation. Likewise, in cocultures of Kupffer cells and SECs, the presence of the Kupffer cell failed to enhance endothelial injury following hypoxia-reoxygenation, and these cocultures did not produce superoxide after reoxygenation. Thus, despite other evidence that Kupffer cells are activated in the intact liver during reperfusion injury, when present in isolation, only endothelial cells possess the innate capacity to undergo hypoxia-reoxygenation injury. Furthermore, changes in oxygen tension alone are not sufficient to activate Kupffer cells to secrete superoxides or other cell products that are toxic to hepatocytes or endothelial cells. It is concluded that SECs play a central role in hypoxia-reoxygenation injury, and the factors that activate Kupffer cells in vivo require further study.
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PMID:The central role of sinusoidal endothelial cells in hepatic hypoxia-reoxygenation injury in the rat. 890 3

Recent studies demonstrate that taurine chloramine (Tau-Cl) inhibits production of nitric oxide (NO) and other proinflammatory mediators in cultured macrophages when added to the media at the time of activation. Because Tau-Cl may react with various media constituents and it is difficult to measure Tau-Cl in complex solutions, we designed experiments to more carefully control cell exposure to various chloramines and NaOCl. RAW 264.7 cells were exposed to 1 mM of NaOCl, Tau-Cl, or chloramine preparations of the following amino acids: L-alanine (L-Ala-Cl), beta-alanine (beta-Ala-Cl), serine (Ser-Cl), or glycine (Gly-Cl) in Hanks' balanced salt solution (HBSS) for up to 2 h (37 degrees C, 5% CO2). The HBSS solution was then replaced with complete media containing interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) for an additional 24 h before measuring cell viability. The chemical stability of NaOCl and each chloramine was evaluated after various times of preactivation exposure by measuring retention of each solution's UV absorption spectra and ability to oxidize KI. Cytotoxicity of each solution was evaluated by the maintained ability of RAW 264.7 cells to reduce MTT. Whereas Tau-Cl, beta-Ala-Cl, and Gly-Cl were stable chloramines, only Tau-Cl was not cytotoxic. L-Ala-Cl, Ser-Cl, and the highly reactive oxidant NaOCl were unstable and toxic. In further studies RAW 264.7 cells were exposed to Tau-Cl in HBSS for 2 h and the solution was then replaced with complete media containing IFN-gamma and LPS, taxol, lipoarabinomannan, or interleukin-2. Production of NO was measured 24 h later and was inhibited in activated cells that were previously exposed to Tau-Cl. Inhibition of NO production was dependent on Tau-Cl concentration and was accounted for by reduced expression of inducible nitric oxide synthase mRNA, regardless of activator combinations. These results support the idea that Tau-Cl has the potential to function as an inhibitory modulator of inflammations.
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PMID:Preactivation exposure of RAW 264.7 cells to taurine chloramine attenuates subsequent production of nitric oxide and expression of iNOS mRNA. 902 21


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