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)

Chemokines have been implicated in the pathogenesis of many inflammatory processes, including bronchopulmonary dysplasia in mechanically ventilated premature infants. We hypothesized that early expression of the proinflammatory cytokine, tumor necrosis factor alpha (TNFalpha), would be followed by later expression of the downstream chemokine, Grobeta, in the oxygen-injured newborn lung. Reverse transcriptase-polymerase chain reaction (RT-PCR) and ribonuclease protection assay (RPA) were used to assess TNFalpha and Grobeta mRNA expression in lung RNA samples from newborn rabbits exposed to > 95% O2 for 8-9 days, followed by 60% O2 for a further 2-4 weeks or from control rabbits exposed to air. Four lung samples per condition were collected every 2 days from day 0 to day 14, and at days 22 and 36. Rabbit alveolar macrophages (AM) stimulated in vitro with bacterial lipopolysaccharide served as positive controls ( n = 8). Grobeta mRNA expression in rabbit lung samples increased with oxygen exposure until day 8, then returned toward baseline levels. This corresponded to previously described elevations in neutrophil number in the lungs. TNFalpha mRNA expression in lung samples was below the limit of detection by RPA and showed no upregulation in hyperoxic lung samples by RT-PCR. TNFalpha activity was assessed in lung lavage ( n = 2 samples per condition per time) using an L929 cell line bioassay and was not increased in hyperoxic animals. The expression of Grobeta mRNA without antecedent or concurrent TNFalpha mRNA expression or activity makes it unlikely that Grobeta in the hyperoxic newborn rabbit lung is elaborated in response to a stimulus by TNFalpha.
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PMID:Effects of hyperoxia on tumor necrosis factor alpha and Grobeta expression in newborn rabbit lungs. 1474 38

Leishmania spp. are protozoans that survive and replicate intracellularly in mammalian macrophages. Antileishmanial immunity requires gamma interferon (IFN-gamma)-mediated macrophage activation and generation of microbicidal effector molecules. The presence of intracellular Leishmania sp. impairs macrophage responses to IFN-gamma, which has led to the description of macrophages as deactivated. It has recently become apparent that in addition to classical activation, macrophages can be activated by distinct triggers to express noninflammatory or anti-inflammatory genes. These nonclassical activation programs have been called alternative or type II pathways. We hypothesized that during initial contact with a phagocyte, leishmaniae activate one of these nonclassical pathways, resulting in expression of genes whose products suppress microbicidal responses. Using DNA microarrays, we studied gene expression in RNAs from BALB/c bone marrow macrophages with and without Leishmania chagasi infection. Some changes were verified by an RNase protection assay, reverse transcription-PCR, immunoblotting, or a bioassay. The pattern of genes activated by leishmania phagocytosis differed from the pattern of genes activated by bacteria or lipopolysaccharide and IFN-gamma. Genes encoding some proinflammatory cytokines, receptors, and Th1-type immune response genes were down-modulated, and some genes associated with anti-inflammatory or Th2-like immune responses were up-regulated. Nonetheless, some markers of alternative (arginase) or type II activation (interleukin-10, tumor necrosis factor alpha) were unchanged. These data suggest that macrophages infected with L. chagasi exhibit a hybrid activation profile that is more characteristic of alternative or type II activation than of classical activation but does not strictly fall into either of these categories. We speculate that the pattern of genes upregulated by leishmania phagocytosis optimizes the chance of parasite survival in this hostile environment.
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PMID:Novel program of macrophage gene expression induced by phagocytosis of Leishmania chagasi. 1503 33

Age appears to be a critical variable in the ability of the lung to cope with external stress. Alterations in cellular responses associated with environmental toxicants are likely to modify the developmental processes. This would suggest that the timing and interaction between exposure and developmental events appears to play an important role as susceptible targets for environmental perturbation. C57BL/6 mice ages 2, 4, 7, 10, 14, 28, and 56 days were exposed to 2.5 PPM ozone for 4 hours or to a 10-minute inhalation of lipopolysaccharide (LPS) with an estimated deposited dose of 26 EU and examined 2 hours post exposure. Abundance of proinflammatory cytokine and chemokine mRNA were measured by RNase protection assay. After ozone exposure interleukin (IL)-6 was not detected in 2-, 4-, and 7-day-old mice; however, increases of 18- to 20-fold were measured in 10-, 14-, 28-, and 56-day-old mice. Macrophage inhibitory protein (MIP)-2 and cytokine-induced neutrophil chenocettractant (KC) were elevated slightly, with no differences between 2- and 56-day-old mice. After LPS exposure, IL-6 was not detected in 2- and 4-day-old mice; however, 8- to 10-fold increases were measured in 7-, 14-, and 28-day-old mice and approximately 20-fold in 56-day-old mice. IL-1beta was elevated approximately 4-fold at 2 and 4 days of age but was elevated 25- to 30-fold in 7-, 14-, 28-, and 56-day-old mice. MIP-2 and KC mRNA abundance was elevated 25- to 30-fold, with no differences between 2- and 56-day-old mice. These results demonstrate that critical time points exist during lung development to inhaled environmental pollutants and that differences exist in the maturation of inflammatory and epithelial defense mechanisms.
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PMID:Differential proinflammatory cytokine responses of the lung to ozone and lipopolysaccharide exposure during postnatal development. 1537 Oct 95

Endotoxin [lipopolysaccharide (LPS)] from Gram-negative bacteria is found in amniotic fluid in intrauterine infections that associate with the risk for spontaneous premature birth, bronchopulmonary dysplasia (BPD), and respiratory distress syndrome. Toll-like receptor 4 (TLR4) is the signaling receptor for LPS. The aim was to investigate the primary inflammatory response in mice shortly after administration of LPS to the dam (14 and 17 d of pregnancy), to the newborn, or into the amniotic fluid. The expression levels of TLR4, IL-1, tumor necrosis factor-alpha, IL-6, IL-10, macrophage inflammatory protein-2, and IL-1 receptor 1 were studied with ribonuclease protection assay. In addition, TLR4 protein was analyzed with Western blotting. The fetal membranes expressed TLR4 mRNA and protein and showed an acute cytokine response to LPS when LPS was administrated into the amniotic fluid. There was distinct ontogeny in the responsiveness of fetal lung to LPS: on fetal day 14 (term 20 d), both the expression of TLR4 and the acute cytokine response were undetectable 5 h after LPS; they became detectable by fetal day 17. TLR4 and the cytokine response further increased after birth. In maternal lung, the TLR4 expression was strongest and up-regulated in parallel with the induction of the cytokines. We propose that TLR4 controls the magnitude of the LPS-induced cytokine response during the perinatal period.
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PMID:Expression of toll-like receptor 4 and endotoxin responsiveness in mice during perinatal period. 1571 65

To study the effect of septicaemia, the temporal changes in tissue adrenomedullin (AM) and preproAM mRNA levels were studied in the heart and blood vessels after lipopolysaccharide (LPS) injection. Radioimmunoassay and solution hybridization-RNase protection assays were used to follow the changes in AM and its mRNA levels respectively after intraperitoneal injection of 10 mg/kg LPS in rats. The preproAM mRNA levels increased at 1 h in the right atrium after LPS injection, while the AM contents decreased at 1 h in the left atrium. The preproAM mRNA levels increased at 3 and 6 h in the left ventricle, whereas it increased at 6 h in the right ventricles after LPS injection. There was an increase in preproAM mRNA levels at 1 and 3 h in the mesenteric artery, while AM levels were increased at 1, 3 and 6 h. However, there were no such changes in the thoracic aorta. There were also increases in tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 in the heart, and in the mesenteric artery (TNF-alpha and IL-1beta) and in thoracic aorta (IL-1beta and IL-6). The present results suggest that the biosynthesis and secretion of AM may be increased in cardiovascular tissues of rats injected with LPS, and that AM may play multiple roles in inflammation.
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PMID:Adrenomedullin gene expression and levels in the cardiovascular system after treatment with lipopolysaccharide. 1575 40

Sequential exposures to inhaled environmental pollutants may result in injuries/responses not predicted by evaluating exposures to an individual toxicant. This may indicate that the lung is damaged or primed by earlier events, so exposure to a nontoxic dose of an environmental pollutant may be sufficient to trigger adverse responses. The present study was designed to test the hypothesis that stimulating lung epithelial damage or inflammatory cell activation followed by a second stimulus leads to responses not seen after individual exposures in the postnatal lung. C57Bl/6 mice ages 4, 10, and 56 days were exposed to either a 10-minute inhalation of lipopolysaccharide (LPS), with an estimated deposited dose of 26 EU, followed immediately by 2.5 PPM ozone for 4 hours, or to 2.5 PPM ozone for 4 hours followed immediately by a 10-minute inhalation of LPS and examined 2 hours post exposure. Abundance of proinflammatory cytokine messages was measured by RNase protection assay. Exposure to LPS followed by ozone induced an inflammatory response in 4-day-old mice, which was not detected after LPS or ozone exposure alone. This exposure sequence also generated a synergistic increase in interleukin (IL)-6 mRNA abundance in 10- and 56-day-old mice but not in 4-day-old mice. Exposure to ozone followed by LPS inhibited IL-1alpha and IL-1beta responses in 4-, 10-, and 56-day-old mice; furthermore, this inhibitory effect was observed after 1.0 and 0.5 PPM ozone exposures. These results demonstrate that preexposure to LPS, which primarily activates inflammatory cell recruitment, can cause sensitization to a secondary stimulus. However, preexposure to ozone, which primarily damages the epithelium, inhibited proinflammatory responses. Thus it was concluded that sequential exposures to ozone and LPS resulted in responses not predicted by evaluating individual exposures during postnatal lung development.
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PMID:Sequential exposures to ozone and lipopolysaccharide in postnatal lung enhance or inhibit cytokine responses. 1602 23

Endothelial cells are highly sensitive to changes in the extracellular milieu. Sepsis results in activation of inflammatory and coagulation pathways. We hypothesized that sepsis-associated mediators may alter the response capacity (so-called "set point") of endothelial cells. Human umbilical vein endothelial cells (HUVEC) were preincubated in the presence or absence of tumor necrosis factor (TNF)-alpha, lipopolysaccharide (LPS), hypoxia, hyperthermia, and/or high glucose; treated with or without thrombin for 4 h; and then processed for RNase protection assays of selected activation markers. Priming with TNF-alpha and LPS significantly inhibited thrombin-mediated induction of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, tissue factor, and E-selectin, but not platelet-derived growth factor-A or CD44. In electrophoretic mobility shift assays, thrombin-treated HUVEC demonstrated inducible binding of p65 NF-kappaB, an effect that was significantly blunted by pretreatment of cells with TNF-alpha and LPS. Consistent with these results, TNF-alpha and LPS attenuated the effect of thrombin on IkappaB phosphorylation, total cytoplasmic IkappaB, and nuclear translocation of p65 NF-kappaB. The inhibitory effect of TNF-alpha on thrombin signaling persisted for up to 24 h following removal of the cytokine. Taken together, these data suggest that inflammatory mediators prime endothelial cells to modulate subsequent thrombin response.
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PMID:Preconditioning of primary human endothelial cells with inflammatory mediators alters the "set point" of the cell. 1617 86

The aim of the present study was to determine the temporal changes in tissue adrenomedullin (AM) and cytokine contents and cytokine and preproAM mRNA levels in the kidney, liver, adrenal gland and spleen of lipopolysaccharide (LPS)-treated rats. Rats were injected with LPS (10 mg/kg, i.p.). Radioimmunoassay and solution hybridization-RNase protection assays were used to follow the changes in AM and its mRNA levels, respectively; ELISA and reverse transcription-polymerase chain reaction were used to follow the changes in cytokines and their mRNA levels, respectively. In the kidney, the preproAM mRNA levels were increased 1 and 3 h after LPS treatment, whereas AM levels were decreased at 3 h. Interleukin (IL)-6 and IL-1beta levels were increased at 3 and 6 h, respectively. The preproAM mRNA levels were elevated in the liver 3 h after LPS injection. Concentrations of tumour necrosis factor (TNF)-alpha and IL-1beta were increased at l and 6 h, respectively. There were no changes in the levels of either preproAM mRNA or AM in the adrenal gland and the spleen. In the spleen, TNF-alpha levels were elevated at 1 and 3 h after LPS injection and IL-1beta was elevated at 1 and 6 h after LPS injection, whereas in the adrenal gland IL-1beta was elevated at 6 h after injection. The mRNA levels of the three cytokines were elevated at all three time intervals examined in the kidney, liver, adrenal gland and spleen, with the exception that TNF-alpha mRNA was not elevated in the adrenal gland at 6 h after LPS injection and IL-1beta mRNA was not elevated in the spleen at 3 and 6 h. The plasma concentrations of TNF-alpha were increased at 1 and 3 h after LPS injection, whereas plasma concentration of IL-1beta and IL-6 were elevated at 3 and 6 h for both. The present results suggest that the biosynthesis and secretion of AM may be differentially regulated in various tissues of rats injected with LPS and that AM may interact with cytokines during inflammation.
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PMID:Differential induction of adrenomedullin, interleukins and tumour necrosis factor-alpha by lipopolysaccharide in rat tissues in vivo. 1644 78

Exposure to environmental pollutants may severely affect lung growth and development. The present study was designed to test the hypothesis that lung damage caused either by ozone or lipopolysaccharide (LPS) occurs through distinct early responses, which are age dependent in the postnatal lung. C57Bl/6 mice ages 4, 10, and 56 days were exposed to inhalation of LPS with an estimated deposited dose of 26 EU and examined 0.5, 1, or 4 h post inhalation exposure; or to 1 or 2.5 ppm ozone for 4 h or sequential exposures of LPS followed by ozone. Abundance of c-fos, c-jun, interleukin (IL)-1beta, Toll-like receptor (TLR) 2, TLR 4, and tumor necrosis factor (TNF) alpha message levels were measured by RNase protection assay. Exposure to ozone for 4 h induced a c-fos and c-jun response in 4-; 10-; and 56-day-old mice in a dose-dependent manner, was localized to conducting and terminal airways, and also induced TLR 4 message abundance in 10- and 56-day-old mice. Exposure to LPS induced c-fos and c-jun 30 and 60 min postinhalation in 10- and 56-day-old mice only. TLR 2 and 4 message abundance was increased at 10 and 56 days, but was undetectable at 4 days of age, and correlated with proinflamatory message induction. Exposure to LPS followed by ozone increased message abundance of IL-1beta, TNFalpha, TLR 2, TLR 4, and c-jun/c-fos at 10 and 56 days, suggesting that combined exposures that induce cellular stresses can regulate gene expression by activating signaling pathways that operate through both transcription factors activator protein (AP)-1 and nuclear factor (NF)-kappaB. However, only c-jun/c-fos and TNFalpha were elevated in 4-day-old mice after sequential exposures, suggesting that the early activation of the inflammatory response after sequential exposures may occur through a TLR-independent pathway. These results suggest that sequential exposures induce multiple signaling pathways that are age dependent.
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PMID:Postnatal lung development: immediate-early gene responses post ozone and LPS exposure. 1686 5

Interleukin-6 (IL-6) has been shown to rescue enterocytes from hypoxia-induced apoptosis when given orally following hemorrhagic shock. In vitro models using an intestinal epithelial cell line (IEC-6) cultured with lipopolysaccharide (LPS) under low O2 conditions, to mimic intestinal conditions, show that these cells also undergo apoptosis, which can be reduced by subsequent culture with IL-6. To examine further the mechanisms of rescue, we cultured normal rat intestinal epithelial cells (IEC-6) under both normoxic and hypoxic conditions and analyzed their responses to LPS and IL-6. We showed that IEC-6 expressed IL-6 receptor on its surface. Further, IEC-6 cells could be rescued from hypoxia-induced apoptosis by co-culture with IL-6. RNase protection assay (RPA) examination revealed that under hypoxic conditions, IEC-6 cells that were resistant to apoptosis showed reduced fas expression and increased bcl-2 expression after co-culture with LPS+IL-6.
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PMID:IL-6 protects enterocytes from hypoxia-induced apoptosis by induction of bcl-2 mRNA and reduction of fas mRNA. 1687 Jan 48


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