Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyper or hypoxia may affect the immune system's chemokine production. Monocyte chemotactic protein-1 (MCP-1), an important chemotactic cytokine can be activated by active oxygen species. Groups of rats were exposed to hypoxic and hyperoxic environmental conditions for 60 h and MCP-1 was determined in their peripheral blood mononuclear cells by Elisa and Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). In this study we evaluated if the ability of monocytes to produce MCP-1 under basal conditions or after stimulation with lipopolysaccharide (LPS) or phytohaemagglutinin (PHA) was differently affected by exposure to hyper or hypoxic conditions in young and aged rats. MCP-1 expression and production in monocyte/macrophages from rats at normoxic conditions was reduced in aged subjects. However, spontaneous, LPS or PHA-induced MCP-1 production was up-regulated by exposure to hyperoxic conditions in both young (62 +/- 8, 99 +/- 7, 102 +/- 8 pg/ml, respectively) and aged rats (79 +/- 4, 112 +/- 9, 117 +/- 10 pg/ ml, respectively). We conclude that hyperoxia is an important regulator of MCP-1 release and support the hypothesis that increased % of O2 may serve to initiate MCP-1 production which then serves to recruit and regulate the distribution of mononuclear cells to the sites of inflammation.
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PMID:Oxygen supply modulates MCP-1 release in monocytes from young and aged rats: decrease of MCP-1 transcription and translation is age-related. 1287 Jun 48

The alveolar macrophage is an important source of interleukin (IL)-8 during pulmonary injury. The IL-8 gene promoter sequence contains nuclear factor (NF)-kappa B, NF-IL6, and activator protein (AP)-1 binding sequences. These sites may have differing regulatory roles in hyperoxia-exposed macrophages than in those stimulated by bacterial lipopolysaccharide (LPS). U-937 and THP-1 macrophage-like cells were exposed to air-5% CO2 or 95% O2-5% CO2, with or without 1.0 microg/ml of LPS, and transfected with an IL-8 promoter-reporter containing NF-kappa B, NF-IL6, or AP-1 mutations. Hyperoxia and LPS caused additive increases in IL-8 production by U-937 cells, whereas THP-1 cells responded only to LPS. An NF-kappa B mutation ablated baseline and O2- and LPS-stimulated reporter activity in both cell lines, whereas NF-IL6 mutations had little effect. An AP-1 mutation had an intermediate effect. LPS, but not hyperoxia, stimulated nuclear translocation of NF-kappa B in both cell lines. Pharmacological blockade of NF-kappa B nuclear translocation ablated LPS-, but not hyperoxia-, stimulated IL-8 production. Although an intact promoter NF-kappa B site is crucial to macrophage IL-8 production, only LPS-stimulated production appears to require additional nuclear translocation of NF-kappa B.
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PMID:Differential roles for NF-kappa B in endotoxin and oxygen induction of interleukin-8 in the macrophage. 1290 91

Hyperbaric oxygen (HBO) is 100% oxygen administered at elevated atmospheric pressure to patients with inflammatory diseases. We developed an in vitro model to investigate the effects of HBO on stimulus-induced proinflammatory cytokine transcription and translation. Human blood-derived monocyte-macrophages were stimulated before being transferred to an HBO chamber where they were incubated at 97.9% O2, 2.1% CO2, 2.4 atmospheres absolute, 37 degrees C. Controls were maintained in the same warm room at normoxia at sea level, hyperoxia or increased pressure alone. A 90-min HBO exposure inhibited IL-1beta synthesized in response to lipopolysaccharide by 23%, lipid A by 45%, phytohaemagglutinin A (PHA) by 68%, and tumour necrosis factor (TNF)-alpha by 27%. HBO suppressed lipopolysaccharide-, lipid A- and PHA-induced TNF-alpha by 29%, 31% and 62%, respectively. HBO transiently reduced PHA-induced steady state IL-1beta mRNA levels. Hyperoxia alone and pressure alone did not affect cytokine production. The immunosuppressive effect of HBO was no longer evident in monocyte-macrophages exposed to HBO for more than 3 h. Interestingly, cells exposed to HBO for 12 h synthesized more IL-1beta than cells cultured under control conditions. In summary, HBO exposure transiently suppresses stimulus-induced proinflammatory cytokine production and steady state RNA levels.
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PMID:Hyperbaric oxygen inhibits stimulus-induced proinflammatory cytokine synthesis by human blood-derived monocyte-macrophages. 1297 55

During respiratory cycles, airborne particles and pathogens are inhaled into the lung, which can cause cytokine production by respiratory macrophages and inflammatory responses. Secreted cytokines affect surfactant protein expression and homeostasis in the lung. In coculturing experiments in vitro, bronchoalveolar macrophages stimulated human surfactant protein B (hSP-B) gene transcription in primary alveolar type II epithelial cells in lipopolysaccharide-independent and -dependent ways. Neutralization by IL-6 antibody abolished lipopolysaccharide-dependent macrophage stimulation of hSP-B gene transcription. IL-6 treatment enhanced signal transducer and activator of transcription (Stat)3 phosphorylation at Y705 in alveolar type II epithelial cells and Clara cells in vivo. Biochemical analysis of functional domain swapping between Stat1 and Stat3 identified that the SH2 domain and the DNA binding domain are critical for Stat3 stimulation of hSP-B gene transcription. Glutathione-S-transferase pull-down study determined functional domains required for protein-protein interaction between Stat3 and retinoic acid receptor-alpha. Cotransfection of Stat3 and retinoic acid receptor-alpha into respiratory epithelial cells resulted in synergistic DNA binding and transcriptional activation on the hSP-B gene. To assess Stat3 physiological function, overexpression of a dominant negative Stat3 in respiratory epithelial cells in a doxycycline-controlled double transgenic mouse line caused pulmonary emphysema and increase of animal death during hyperoxia. Therefore, the IL-6/Stat3 signaling axis plays an important role in surfactant protein homeostasis and respiratory inflammation in the lung.
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PMID:Synergy between signal transducer and activator of transcription 3 and retinoic acid receptor-alpha in regulation of the surfactant protein B gene in the lung. 1504 88

An imbalance in matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) leads to excessive or insufficient tissue breakdown, which is associated with many disease processes. The TIMP-3 null mouse is a model of MMP/TIMP imbalance, which develops air space enlargement and decreased lung function. These mice responded differently to cecal ligation and perforation (CLP)-induced septic lung injury than wild-type controls. The current study addresses whether the TIMP-3 knockout lung is susceptible to different types of insults or only those involving sepsis, by examining its response to lipopolysaccharide (LPS)-induced sepsis, mechanical ventilation (MV), and hyperoxia. TIMP-3 null noninjured controls of each insult consistently demonstrated significantly higher compliance vs. wild-type mice. Null mice treated with LPS had a further significantly increased compliance compared with untreated controls. Conversely, MV and hyperoxia did not alter compliance in the null lung. MMP abundance and activity increased in response to LPS but were generally unaltered following MV or hyperoxia, correlating with compliance alterations. All three insults produced inflammatory cytokines; however, the response of the null vs. wild-type lung was dependent on the type of insult. Overall, this study demonstrated that 1) LPS-induced sepsis produced a similar response in null mice to CLP-induced sepsis, 2) the null lung responded differently to various insults, and 3) the null susceptibility to compliance changes correlated with increased MMPs. In conclusion, this study provides insight into the role of TIMP-3 in response to various lung insults, specifically its importance in regulating MMPs to maintain compliance during a sepsis.
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PMID:Differential response of TIMP-3 null mice to the lung insults of sepsis, mechanical ventilation, and hyperoxia. 1580 39

Flaxseed (FS) is a nutritional supplement with high concentrations of (n-3) fatty acids and lignans that have anti-inflammatory and antioxidant properties. The use of FS in the prevention or treatment of acute lung disease is unknown. In this study, we evaluated diets with high FS content in experimental murine models of acute lung injury and inflammation. The kinetics of lignan accumulation in blood, following 10% FS supplementation, was determined using liquid chromatography tandem mass spectrometry. Mice were fed isocaloric control and 10% FS-supplemented diets for at least 3 wk and challenged by hyperoxia (80% oxygen), intratracheal instillation of lipopolysaccharide, or acid aspiration. Bronchoalveolar lavage was evaluated for white blood cells, neutrophils, and proteins after a 24 h postintratracheal challenge of hydrochloric acid or lipopolysaccharide, or after 6 d of hyperoxia. Lung lipid peroxidation was assessed by tissue malondialdehyde concentrations. The plasma concentrations of the FS lignans, enterodiol and enterolactone, were stable after mice had eaten the diets for 2 wk. Following hyperoxia and acid aspiration, bronchoalveolar lavage neutrophils decreased in FS-supplemented mice (P = 0.012 and P = 0.027, respectively), whereas overall alveolar white blood cell influx tended to be lower (P = 0.11). In contrast, neither lung injury nor inflammation was ameliorated by FS following lipopolysaccharide instillation. Lung malondialdehyde levels were lower in hyperoxic mice than in unchallenged mice (P = 0.0001), and decreased with FS treatment following acid aspiration (P = 0.011). Dietary FS decreased lung inflammation and lipid peroxidation, suggesting a protective role against pro-oxidant-induced tissue damage in vivo.
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PMID:Dietary flaxseed supplementation ameliorates inflammation and oxidative tissue damage in experimental models of acute lung injury in mice. 1670 19

We previously demonstrated that hyperbaric oxygen (HBO) treatment alleviated lipopolysaccharide (LPS)-induced acute lung injury in rats. However, the mechanisms responsible for the protective effect are still not fully understood. To obtain further information on the protective effect of HBO, in this study we investigated the role of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in intratracheal spraying LPS-induced acute lung injury in rats after HBO or hyperoxia treatment. The results showed that HBO but not hyperoxia attenuated the TNF-alpha level in plasma and bronchoalveolar lavage (BAL) fluid, NO concentration in BAL and plasma, and inducible NO synthase protein expression in lung tissue based on the Western blotting and immunohistochemical staining.
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PMID:Influence of hyperbaric oxygen on tumor necrosis factor-alpha and nitric oxide production in endotoxin-induced acute lung injury in rats. 1704 93

Noni juice possesses antioxidant activity and prevents superoxide-mediated tissue injury in laboratory animals. A polysaccharide-rich precipitate of noni juice (noni-ppt) also stimulates tumor necrosis factor (TNF) and interleukin 1 (IL-1) in mice. Endotoxin (lipopolysaccharide) stimulates TNF and IL-1 in rats and protects against superoxide-mediated oxygen toxicity. Accordingly, we hypothesized that noni juice, or noni-ppt, would protect rats against pulmonary oxygen toxicity. Rats were divided into four groups; one received noni-ppt to test for cytokine-induced protection; another received noni juice to test for antioxidant activity; a third received saline as hyperoxia control; a fourth received no treatment in air. Rats were then exposed to either hyperoxia (> 97% oxygen at sea level for 52 or 60 hours) or air and lung injury assessed. Rats receiving saline, noni-ppt or noni juice exhibited typical signs of oxygen toxicity with hemorrhagic lungs, large pleural effusions and increases in protein concentration in bronchoalveolar lavage fluid. They also developed heavy lungs with increases in wet/dry weight ratios, hematocrit values and ratios of effusion protein to plasma protein concentration. These results show that Noni juice and Noni-ppt do not prevent oxygen toxicity in rats when administered according to the protocols used in this study.
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PMID:Failure of juice or juice extract from the noni plant (Morinda citrifolia) to protect rats against oxygen toxicity. 1739 17

Pulmonary vascular endothelial injury resulting from lipopolysaccharide (LPS) and oxygen toxicity contributes to vascular simplification seen in the lungs of premature infants with bronchopulmonary dysplasia. Whether the severity of endotoxin-induced endothelial injury is modulated by ambient oxygen tension (hypoxic intrauterine environment vs. hyperoxic postnatal environment) remains unknown. We posited that ovine fetal pulmonary artery endothelial cells (FPAEC) will be more resistant to LPS toxicity under hypoxic conditions (20-25 Torr) mimicking the fetal milieu. LPS (10 microg/ml) inhibited FPAEC proliferation and induced apoptosis under normoxic conditions (21% O(2)) in vitro. LPS-induced FPAEC apoptosis was attenuated in hypoxia (5% O(2)) and exacerbated by hyperoxia (55% O(2)). LPS increased intracellular superoxide formation, as measured by 2-hydroxyethidium (2-HE) formation, in FPAEC in normoxia and hypoxia. 2-HE formation in LPS-treated FPAEC increased in parallel with the severity of LPS-induced apoptosis in FPAEC, increasing from hypoxia to normoxia to hyperoxia. Differences in LPS-induced apoptosis between hypoxia and normoxia were abolished when LPS-treated FPAEC incubated in hypoxia were pretreated with menadione to increase superoxide production. Apocynin decreased 2-HE formation, and attenuated LPS-induced FPAEC apoptosis under normoxic conditions. We conclude that ambient oxygen concentration modulates the severity of LPS-mediated injury in FPAEC by regulating superoxide levels produced in response to LPS.
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PMID:Attenuation of lipopolysaccharide-induced oxidative stress and apoptosis in fetal pulmonary artery endothelial cells by hypoxia. 1913 25

Antenatal inflammation is a known risk factor of bronchopulmonary dysplasia. The authors hypothesized that lipopolysaccharide (LPS) administration amplifies hyperoxia-induced lung injury in neonatal rats. LPS (0.5 or 1.0 microg) or normal saline was injected into the amniotic sacs of pregnant rats at 20 d gestation (term 22.5 d). After birth, rats were exposed to 85% oxygen or room air for 1 or 2 wk. Morphometric analysis of lungs was performed on 14 d. One week of hyperoxia without LPS administration resulted in modest lung injury. LPS at 0.5 microg alone did not alter lung morphology, but amplified the effect of 1 wk of hyperoxia resulting in marked inhibition of alveolarization (airspaces were enlarged and alveolar surface areas further reduced). LPS at 1.0 microg independently induced modest lung injury and also amplified the effect of 1 wk of hyperoxia. However, this sensitizing effect of LPS was not observed in rats subjected to 2 wks of hyperoxia, which in itself caused extensive lung injury (possibly masking the effect of LPS). The authors concluded that intra-amniotic LPS sensitizes neonatal rat lungs, and thus, amplifies the hyperoxia-induced inhibition of alveolarization.
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PMID:Bronchopulmonary dysplasia in a rat model induced by intra-amniotic inflammation and postnatal hyperoxia: morphometric aspects. 1939 Dec 5


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