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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 inducible nitric oxide (NO) synthase gene in alveolar macrophages (AMs) is a stress response gene that may contribute to tissue injury in the lung after respiration with high O(2) concentrations through extensive production of NO. In this study, we investigated the influence of hyperoxia on the NO pathway in rat AMs in vitro, its regulation by the transcription factors nuclear factor (NF)-kappaB and activator protein (AP)-1, and the role of reactive oxygen species (ROS). AMs were treated with lipopolysaccharide (LPS) and/or interferon (IFN)-gamma and incubated under 21 or 85% O(2). Stimulation with LPS and IFN-gamma led to induction of the NO pathway that was further upregulated by hyperoxia. The binding activity of NF-kappaB, in contrast to that of AP-1, was activated on stimulation with LPS and IFN-gamma, and both were further increased under hyperoxia. The antioxidants pyrrolidine dithiocarbamate and N-acetyl-L-cysteine inhibited intracellular ROS production and the NO pathway under both normoxic and hyperoxic conditions but had diverse effects on the transcription factors. The results presented here indicate that hyperoxia can upregulate the NO pathway in stimulated AMs through increased production of intracellular ROS and activation of NF-kappaB and AP-1.
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PMID:Hyperoxia upregulates the NO pathway in alveolar macrophages in vitro: role of AP-1 and NF-kappaB. 1129 May 14

Hyperoxia-induced lung injury complicates the care of many critically ill patients who receive supplemental oxygen therapy. Hyperoxic injury to lung tissues is mediated by reactive oxygen species, inflammatory cell activation, and release of cytotoxic cytokines. IFN-gamma is known to be induced in lungs exposed to high concentrations of oxygen; however, its contribution to hyperoxia-induced lung injury remains unclear. To determine whether IFN-gamma contributes to hyperoxia-induced lung injury, we first used anti-mouse IFN-gamma antibody to blockade IFN-gamma activity. Administration of anti-mouse IFN-gamma antibody inhibited hyperoxia-induced increases in pulmonary alveolar permeability and neutrophil migration into lung air spaces. To confirm that IFN-gamma contributes to hyperoxic lung injury, we then simultaneously exposed IFN-gamma-deficient (IFN-gamma-/-) mice and wild-type mice to hyperoxia. In the early phase of hyperoxia, permeability changes and neutrophil migration were significantly reduced in IFN-gamma-/- mice compared with wild-type mice, although the differences in permeability changes and neutrophil migration between IFN-gamma-/- mice and wild-type mice were not significant in the late phase of hyperoxia. The concentrations of IL-12 and IL-18, two cytokines that play a role in IFN-gamma induction, significantly increased in bronchoalveolar lavage fluid after exposure to hyperoxia in both IFN-gamma-/- mice and wild-type mice, suggesting that hyperoxia initiates upstream events that result in IFN-gamma production. Although there was no significant difference in overall survival, IFN-gamma-/- mice had a better early survival rate than did the wild-type mice. Therefore, these data strongly suggest that IFN-gamma is a key molecular contributor to hyperoxia-induced lung injury.
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PMID:Interferon-gamma: a key contributor to hyperoxia-induced lung injury in mice. 1525 86

Cytokines are peptides that are produced by virtually every nucleated cell type in the body, possess overlapping biological activities, exert different effects at different concentrations, can either synergize or antagonize the effects of other cytokines, are regulated in a complex manner, and function via cytokine cascades. Hyperoxia-induced acute lung injury (HALI) is characterized by an influx of inflammatory cells, increased pulmonary permeability, and endothelial and epithelial cell injury/death. Some of these effects are orchestrated by cytokines. There are significant differences in the response of the developing versus the adult lung to hyperoxia. We review here cytokines (and select growth factors) that are involved in tolerance toward HALI in animal models. Increased cytokine expression and release have a cascade effect in HALI. IL-1 precedes the increase in IL-6 and CINC-1/IL-8 and this seems to predate the influx of inflammatory cells. Inflammatory cells in the alveolar space amplify the lung damage. Other cytokines that are primarily involved in this inflammatory response include IFN-gamma, MCP-1, and MIP-2. Certain cytokines (and growth factors) seem to ameliorate HALI by affecting cell death pathways. These include GM-CSF, KGF, IL-11, IL-13, and VEGF. There are significant differences in the type and temporal sequence of cytokine expression and release in the adult and newborn lung in response to hyperoxia. The newborn lung is greatly resistant to hyperoxia compared to the adult. The delayed increase in lung IL-1 and IL-6 in the newborn could induce protective factors that would help in the resolution of hyperoxia-induced injury. Designing a therapeutic approach to counteract oxygen toxicity in the adult and immature lung first needs understanding of the unique responses in each scenario.
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PMID:Cytokines in tolerance to hyperoxia-induced injury in the developing and adult lung. 1678 48