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)

Hyperoxia-associated production of reactive oxygen species leads to neutrophil infiltration into the lungs and increased pulmonary proinflammatory cytokine expression. However, the initial events induced by hyperoxia, and leading to acute inflammatory lung injury, remain incompletely characterized. To explore this issue, we examined nuclear transcriptional regulatory factor (NF-kappaB and NF-IL-6) activation and cytokine expression in the lungs following 12 to 48 h of hyperoxia exposure. No increases in cytokine (IL-1beta, IL-6, IL-10, TGF-beta, TNF-alpha, IFN-gamma) expression nor in NF-kappaB activation were found after 12 h of hyperoxia. Following 24 h of hyperoxia, NF-kappaB activation and increased levels of TNF-alpha mRNA were present in pulmonary lymphocytes. By 48 h of hyperoxia, amounts of IFN-gamma and TNF-alpha protein as well as mRNA were increased in the lungs, and NF-kappaB continued to show activation, even though no histologic abnormalities were present. These results show that hyperoxia activates NF-kappaB in the lungs before any increase in proinflammatory cytokine protein occurs, and suggest that NF-kappaB activation may represent an initial event in the proinflammatory sequence induced by hyperoxia.
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PMID:Hyperoxia activates NF-kappaB and increases TNF-alpha and IFN-gamma gene expression in mouse pulmonary lymphocytes. 889 21

The effects of combined exposure to subthreshold hyperoxia and the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) on the expression of intercellular adhesion molecule-1 (ICAM-1) were examined in bovine lung microvascular endothelial cells (BLuEC). The expression of total ICAM-1 was not affected by 50% hyperoxia conditions alone, indicating that this level is subthreshold for BLuEC. In the presence of 5 ng/mL TNF-alpha, which has minimal influence on BLuEC alone, the amount of total ICAM-1 expression under 50% hyperoxia was higher than that in normoxic conditions (approximately 30%) throughout the culture period. The amount of soluble ICAM-1 that has been released into the culture medium increased after joint exposure to hyperoxia and TNF-alpha. These results suggest that exposure to subthreshold hyperoxia, which does not by itself cause damage to the endothelial cells or induce ICAM-1 expression, potentiates the effects of low-level TNF-alpha exposure.
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PMID:Subthreshold hyperoxia potentiates TNF-alpha-induced ICAM-1 expression on cultured pulmonary microvascular endothelial cells. 918 88

Clara cell secretory protein (CCSP) is an abundant component of the extracellular lining fluid of airways. Even though the in vivo function of CCSP is unknown, in vitro studies support a potential role of CCSP in the control of inflammatory responses. CCSP-deficient mice (CCSP -/-) were generated to investigate the in vivo function of this protein (13). In this study, we used hyperoxia exposure as a model to investigate phenotypic consequences of CCSP deficiency following acute lung injury. The pathologic response of the mouse lung to hyperoxia, and recovery of the lung, include inflammatory cell infiltrate and edema. Continuous exposure to > 95% O2 was associated with significantly reduced survival time among CCSP -/- mice as compared with strain-, age-, and sex-matched wild-type control mice. Differences in survival were associated with early onset of lung edema in CCSP -/- mice as compared with wild-type controls. To further investigate these differences in response, mice were exposed to > 95% O2 for either 48 h or 68 h with one group receiving 68 h of hyperoxia followed by room-air recovery. Lung RNA was characterized for changes in the abundance of cytokine messenger RNA (mRNA) using a ribonuclease (RNase) protection assay. After 68 h of hyperoxia, interleukin-6 (IL-6), IL-1beta, and IL-3 mRNAs were 14-, 3-, and 2.5-fold higher, respectively, in CCSP -/- mice than in similarly exposed wild-type control mice. Increased expression of IL-1beta mRNA in hyperoxia-exposed CCSP -/- mice was localized principally within the lung parenchyma, suggesting that the effects of CCSP deficiency were not confined to the airway epithelium. We conclude that CCSP deficiency results in increased sensitivity to hyperoxia-induced lung injury as measured by increased mortality, early onset of lung edema, and induction of proinflammatory cytokine mRNAs.
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PMID:Altered pulmonary response to hyperoxia in Clara cell secretory protein deficient mice. 927 2

Pulmonary oxygen toxicity occurs after prolonged administration of increased fractions of inspired oxygen. Lung damage in this setting manifests as diffuse alveolar damage. In animals exposed to hyperoxia, increased numbers of alveolar macrophages are noted 72 h after initiation of high concentrations of oxygen. Monocyte chemotactic protein-1 (MCP-1) is a cytokine released by a number of cell types that has potent chemotactic activity for monocytes, precursor cells for alveolar macrophages. In the current study, we examined whether MCP-1 production was increased in response to hyperoxia. We used the monocyte/ histiocytic U937 cell line and exposed these cells to hyperoxia for variable amounts of time, then determined MCP-1 concentrations by enzyme-linked immunosorbent assay and MCP-1 mRNA levels by Northern blot analysis. We also examined the effects of dexamethasone on the response of U937 cells to hyperoxia. Finally, as a potential mechanism for regulation of U937 MCP-1 production, we examined effects of hyperoxia on MCP-1 mRNA stability. The results demonstrate that hyperoxia stimulates MCP-1 production after 6 and 24 h of exposure. MCP-1 mRNA levels are also increased after initiation of hyperoxia in part through effects on MCP-1 transcript stability. Dexamethasone significantly reduces MCP-1 production and mRNA levels also in part through effects on transcript stability. These studies suggest monocytes may be attracted to hyperoxia-exposed lungs through enhanced MCP-1 production. MCP-1 production appears to be upregulated in part through post-transcriptional processes in this setting.
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PMID:Modulation of monocyte chemotactic protein-1 production by hyperoxia: importance of RNA stability in control of cytokine production. 953 39

The pulmonary response to various toxicants including bleomycin, ozone, ionizing radiation, and hyperoxia is highly variable among mouse strains. The current study tests the hypothesis that at a similar stage of injury, regardless of strain, expression of inflammatory cytokine and epithelial marker genes would be similar, indicating a common pathway of injury progression. Three strains of mice, C57B1/6J, 129/J, and C3H/HeJ, ranging from sensitive to resistant, were exposed to > 95% O2 for varying times. Ribonuclease protection was used to quantify changes in cytokine mRNA. Despite differences in the kinetics, each strain demonstrated similar hyperoxia-induced changes in the abundance of interleukin (IL)-6, IL-1 beta, IL-3, and tumor neucrosis factor (TNF)-alpha. For each strain, death was accompanied by similar increases in cytokine mRNAs above steady-state control levels. Other inflammatory cytokines, including IL-1 alpha, IL-4, and interferon (IFN)-gamma, were unaltered in all strains at all times. In situ hybridization analysis of the epithelial markers, surfactant protein B (SPB), and clara cell secretory protein (CCSP) at the time of proinflammatory induction showed a similar pattern of expression in all strains. Increased SPB was detected in bronchiolar epithelium, while the number of type II cells expressing this message declined. Both the number of cells expressing CCSP as well as abundance per cell declined. These results suggest that although differences in acute sensitivity to hyperoxia exist between mouse strains, once initiated, acute epithelial cell injury and associated inflammatory changes follow the same pattern in all strains.
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PMID:Inflammatory and epithelial responses in mouse strains that differ in sensitivity to hyperoxic injury. 955 76

We studied tumor necrosis factor (TNF)-alpha as a candidate cytokine to promote neuroendocrine cell differentiation in a nitrosamine-hyperoxia hamster lung injury model. Differential screening identified expression of the genes modulated by TNF-alpha preceding neuroendocrine cell differentiation. Undifferentiated small cell lung carcinoma (SCLC) cell lines NCI-H82 and NCI-H526 were treated with TNF-alpha for up to 2 wk. Both cell lines demonstrated rapid induction of gastrin-releasing peptide (GRP) mRNA; H82 cells also expressed aromatic-L-amino acid decarboxylase mRNA within 5 min after TNF-alpha was added. Nuclear translocation of nuclear factor-kappaB immunostaining occurred with TNF-alpha treatment, suggesting nuclear factor-kappaB involvement in the induction of GRP and/or aromatic-L-amino acid decarboxylase gene expression. We also demonstrated dense core neurosecretory granules and immunostaining for proGRP and neural cell adhesion molecule in H82 cells after 7-14 days of TNF-alpha treatment. We conclude that TNF-alpha can induce phenotypic features of neuroendocrine cell differentiation in SCLC cell lines. Similar effects of TNF-alpha in vivo may contribute to the neuroendocrine cell differentiation/hyperplasia associated with many chronic inflammatory pulmonary diseases.
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PMID:Tumor necrosis factor induces neuroendocrine differentiation in small cell lung cancer cell lines. 970 92

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that appears to play a significant role in the development of neonatal chronic lung disease (CLD). Inflammation and CLD are also associated with respiratory tract colonization with genital mycoplasmas. The possible protective roles of surfactant in mitigating the inflammatory response to these microbes were investigated. Murine RAW 264.7 macrophages were preincubated with an exogenous surfactant and exposed overnight to sterile media, lipopolysaccharide (LPS), Mycoplasma hominis, or Ureaplasma urealyticum. Macrophages released TNF-alpha in response to challenge with LPS, U. urealyticum, and M. hominis in a concentration-dependent fashion. Surfactant suppressed LPS and M. hominis induced TNF-alpha production in a dose-dependent manner but suppressed U. urealyticum-mediated TNF-alpha production only at the higher dose tested. Similar effects were seen in hyperoxia (95% O2). Thus, exogenous bovine surfactant significantly inhibits the production of TNF-alpha by murine macrophages stimulated with genital mycoplasmas and bacterial LPS.
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PMID:Exogenous bovine surfactant suppresses tumor necrosis factor-alpha release by murine macrophages stimulated by genital mycoplasmas. 980 43

In the development of lung damage induced by oxidative stress, it has been proposed that changes in alveolar macrophages (AM) function with modifications in cytokine production may contribute to altered repair processes. To characterize the changes in profiles of cytokine production by macrophages exposed to oxidants, the effects of hyperoxia (95% O2) on interleukin (IL)-1 beta, IL-6, IL-8, and tumour necrosis factor-alpha (TNF-alpha) expression were studied. Experiments were first performed using AM obtained from control subjects and children with interstitial lung disease. Results showed that a 48 h O2 exposure was associated with two distinct patterns of response: a decrease in TNF-alpha, IL-1 beta and IL-6 expression, and an increase in IL-8. To complete these observations we used U937 cells that were exposed for various durations to hyperoxia. We confirmed that a 48 h O2 exposure led to similar changes with a decrease in TNF-alpha, IL-1 beta and IL-6 production and an increase in IL-8. Interestingly, this cytokine response was preceded during the first hours of O2 treatment by induction of TNF-alpha, IL-1 beta and IL-6. These data indicate that hyperoxia induces changes in the expression of macrophages inflammatory cytokines, and that these modifications appear to be influenced by the duration of O2 exposure.
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PMID:Effect of hyperoxia on human macrophage cytokine response. 1007 May 69

Retinopathy of prematurity (ROP) is characterized by inhibition of the growth of the retinal vessels and subsequent neovascularization. Pharmacologic doses of glucocorticoids are known to decrease growth and to suppress inflammation. The aim of the present study was to investigate whether hyperoxia and/or glucocorticoid affect the growth of the retinal vessels and the expression of the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra). The following treatments were given to newborn rabbits during the rapid growth of retinal vessels: 1) placebo and room air (n = 14); 2) dexamethasone (Dx) at 1 mg/kg/d during d 3 to 8 and room air (n = 14); 3) placebo and 100% oxygen (d 3 to 7) (n = 14); 4) Dx and O2 (n = 16). On d 12, the eyes were studied for retinal vessel length and vascular surface area from India ink-perfused vessels. When indicated, retinas were harvested on d 7 and studied for the expression of IL-1ra mRNA using Northern blot analysis. Hyperoxia decreased the length and area of the retinal vessel complexes (p < 0.01) and induced neovascularization in three of eight animals (38%). Dx decreased the length and area (p < 0.01) and tended to increase the tortuosity of the retinal vessels. Dx did not potentiate the hyperoxia-induced suppression of retinal vessel growth and prevented the hyperoxia-induced neovascularization (p = 0.04). Hyperoxia inhibited the expression of IL-1ra mRNA, whereas Dx ameliorated the hyperoxia-induced suppression of IL-1ra. According to present results, glucocorticoid decreases the retinal vessel growth and may decrease the hyperoxia-induced neovascularization. We propose that immature and damaged retinal vessels are affected by pharmacologic dosage of glucocorticoid.
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PMID:Hyperoxia and glucocorticoid modify retinal vessel growth and interleukin-1 receptor antagonist in newborn rabbits. 1008 47

Lisofylline [1-(5R-hydroxyhexyl)-3,7-dimethylxanthine] decreases lipid peroxidation in vitro and in vivo suppresses proinflammatory cytokine expression in models of lung injury due to sepsis, blood loss, and oxidative damage. In the present experiments, we used a murine hyperoxia model to examine the effects of lisofylline on the activation of nuclear transcriptional regulatory factors [nuclear factor-kappaB and cAMP response element binding protein (CREB)], the expression of proinflammatory cytokines in the lungs, and the circulating levels of oxidized free fatty acids as well as on hyperoxia-induced lung injury and mortality. Treatment with lisofylline inhibited hyperoxia-associated increases in tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in the lungs as well as decreased the levels of hyperoxia-induced serum-oxidized free fatty acids. Although hyperoxic exposure produced activation of both nuclear factor-kappaB and CREB in lung cell populations, only CREB activation was reduced in the mice treated with lisofylline. Lisofylline diminished hyperoxia-associated increases in lung wet-to-dry weight ratios and improved survival in animals exposed to hyperoxia. These results suggest that lisofylline ameliorates hyperoxia-induced lung injury and mortality through inhibiting CREB activation, membrane oxidation, and proinflammatory cytokine expression in the lungs.
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PMID:Effects of lisofylline on hyperoxia-induced lung injury. 1033 34


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