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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antioxidant enzymes, including superoxide dismutase, are important for protecting the lung against O2 injury. Manganese superoxide dismutase (Mn-SOD) is a superoxide anion (O2-.) scavenger located in the mitochondria, a primary site of O2-. production during hyperoxia. We studied the effects of tumor necrosis factor (TNF-alpha), a macrophage-derived cytokine, on Mn-SOD expression in human pulmonary adenocarcinoma cells. TNF-alpha significantly increased Mn-SOD activity and mRNA in a dose-and time-dependent manner. Mn-SOD activity was increased 3-fold and mRNA 20-fold after a 48-h incubation with TNF-alpha (25 ng/ml). To examine the mechanism of this increase, cells were incubated for 48 h with TNF-alpha (25 ng/ml) with or without cycloheximide (10 microns) or actinomycin D (10 micrograms/ml). Actinomycin D blocked the induction of Mn-SOD mRNA by TNF-alpha, but cycloheximide did not. These findings suggest that the effect of TNF-alpha requires gene transcription but not synthesis of new protein intermediates. To test the hypothesis that increased Mn-SOD protects against oxidative injury, pulmonary adenocarcinoma cells were incubated in TNF-alpha (25 ng/ml) for 48 h and then exposed to paraquat (PQ+), an intracellular O2-. generator. Cells pretreated with TNF-alpha had significantly improved survival in PQ+ compared with controls. At the LD50 (6 microns) for control cells, 95% of TNF-alpha-treated cells survived, 85% at the LD75 (10 microns), and 77% at the LD90 (14 microns). Our results suggest that the induction of Mn-SOD by TNF-alpha in pulmonary adenocarcinoma cells is pretranslationally mediated and that increasing Mn-SOD activity with TNF-alpha confers protection against O2 radicals.
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PMID:Tumor necrosis factor-alpha increases Mn-SOD expression: protection against oxidant injury. 185 Feb 7

Rats injected with interleukin-1 (10 micrograms) and tumor necrosis factor (10 micrograms) and then exposed continuously to hyperoxia (greater than 99% O2, 1 atm) survived longer, had increased lung reduced/oxidized glutathione ratios, smaller pleural effusions, less pulmonary hypertension and improved arterial blood gases. The percentage of animals surviving for 72 hours in hyperoxia increased from 8% to 94%. Although relatively small increases in glutathione redox cycle enzymes occurred four and sixteen hours following cytokine injection, dramatic increases in all major antioxidant enzymes including superoxide dismutase, glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and catalase had occurred following 72 hours of exposure to hyperoxia. The protective effect of IL-1 + TNF against lethal pulmonary O2 toxicity could be partially inhibited by pre-injection of lysine acetylsalicylate or, less effectively, of ibuprofen. Recent studies have suggested that both IL-1 and TNF can induce manganese (mitochondrial) superoxide dismutase mRNA and protein synthesis in a variety of cell types. Preliminary studies suggest that IL-1 alone, in ample dosage, can provide protection against lethal pulmonary O2 toxicity. Future studies should be directed toward identification of acute phase changes in lung antioxidant enzymes, surfactant proteins and/or lipid components, enzymes needed for synthesis of surfactant phospholipids, and/or other protective proteins. Additional work also needs to be done in identifying the lung cell types in which early enzyme induction occurs. These studies should provide a better understanding of mechanisms whereby protection against pulmonary O2 toxicity can occur. An understanding of the molecular mechanisms inducing protective proteins should lead to more precise pharmacologic control of these processes.
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PMID:Protection against pulmonary oxygen toxicity by interleukin-1 and tumor necrosis factor: role of antioxidant enzymes and effect of cyclooxygenase inhibitors. 251 82

Transforming growth factor-alpha (TGF alpha) is a cytokine secreted by stimulated alveolar macrophages (AM) in vitro and after in vivo particulate or hyperoxia exposure and has been implicated in the processes of postnatal lung development. It is unknown if AM TGF alpha secretion changes during normal postnatal lung development. After sacrifice of New Zealand white rabbits on postnatal d 0-2, 5-7, 9-10, 14, 21, and 28 and > 4 mo (adult), AM were isolated by discontinuous density centrifugation and placed in culture in the presence or absence of concanavalin A (ConA) for 24 h. Media were collected, and the concentration and isoforms of TGF alpha in AM media samples were determined by an epidermal growth factor/TGF alpha radioreceptor assay and Western immunodetection, respectively. TGF alpha was present in media of AM from the 1.06 and 1.08 g/dL Percoll densities, but not in the 1.10 g/dL density. Statistically significant differences in TGF alpha secretion by unstimulated and ConA-stimulated AM at the various ages were not detected until d 14 (p < 0.02). Western blot analysis of unstimulated AM media samples from d 0-7 rabbits demonstrated the presence of TGF alpha isoforms at 46, 30, and 14.3 kD. At later postnatal ages (> or = d 9), a single 14.3-kD isoform was present. In contrast, analysis of ConA-stimulated AM media samples showed TGF alpha isoforms at 46, 30, and 14.3 kD for all ages; however, the 6-kD mature isoform was present only in juvenile (d 28) and adult media.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secretion of transforming growth factor-alpha (TGF alpha) by postnatal rabbit alveolar macrophages. 747 96

Recent studies have presented evidence that the processes of hypoxaemia and reperfusion are involved in several pathogenetic mechanisms of atherosclerotic lesions. The ability of hypoxaemia to activate circulating white blood cells (WBCs) and enhance WBC-endothelial cell (EC) interactions is suspected to be a major factor in deleterious processes in the blood vessel wall. Various groups have suggested that cell adhesion molecules (CAMs), such as ICAM-1, VCAM-1 and E-selectin and their leukocyte ligands are involved in intercellular activities of the relevant cell types. We studied the effects of different oxygen tensions, simulating normoxic conditions, hypoxia and hyperoxia in vitro with the help of an umbilical vein EC model in order to determine the effects of oxygenation on CAM presentation on vascular ECs with and without further cytokine and endotoxin (lipopolysaccharides; LPS) stimulation. Semiquantitative analysis of ICAM-1, E-selectin and VCAM-1 was performed using cell enzyme immunoassay techniques. The presentation of ICAM-1, E-selectin and VCAM-1 remained on the whole unaffected by both hypoxia and hyperoxic conditioning after both 7 and 24 h. Stimulation of ICAM-1 by cytokines and LPS was only marginally influenced by the oxygen tension. Cytokine induction of E-selectin was not affected after 7 h and was even reduced under hypoxia, compared to the control culture after 24 h, while stimulation was increased by hyperoxia. VCAM-1 was reduced in both the hypoxic and hyperoxic culture, while being maximally stimulated by cytokines and LPS after 7 h. In general, an effect of hypoxia was not found without any further stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative studies on vascular endothelium in vitro. 2. Hypoxia: its influences on endothelial cell proliferation and expression of cell adhesion molecules. 754 71

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

Ventilator-induced lung injury in children and adults is characterized by an initial inflammatory phase. To investigate whether the inflammatory cytokine, IL-1, plays a role in this process, a rabbit model of ventilator-induced injury was created. Animals maintained under pentobarbital anesthesia were primed for injury by undergoing lung lavage with 22 mL/kg of saline and then ventilated for 8 h with either FIO2 0.21 and normal pressures or FIO2 1.0 and high ventilator pressures. The animals exposed to hyperoxia/hyperventilation demonstrated a greater increase in lung lavage neutrophil counts and a higher histological injury score, as well as a faster decline in oxygenation compared to the control animals. A third group of rabbits received 800 micrograms of recombinant IL-1 receptor antagonist after lung lavage and prior to the exposure to FIO2 1.0 and high ventilator pressures. These animals had significantly lower concentrations of albumin and elastase and lower neutrophil counts in their lungs after the 8-h ventilatory period compared to hyperoxia/hyperventilation rabbits. IL-1 blockade had no effect on the decline in dynamic compliance and oxygenation seen in saline-treated hyperoxic/hyperventilated rabbits. IL-1 is a mediator of acute inflammation due to ventilator-induced lung injury.
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PMID:Effect of IL-1 blockade on inflammatory manifestations of acute ventilator-induced lung injury in a rabbit model. 777 27

The significance of manganese superoxide dismutase (MnSOD) induction in cells and tissues during oxidant stress is still poorly understood. In this study, transformed human bronchial epithelial cells (BEAS 2B) were treated with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), or with combination of these cytokines (10 ng/ml concentrations) for 48 or 72 h and exposed to selected oxidants. TNF-alpha and IFN-gamma + TNF-alpha combination resulted in a marked increase of MnSOD protein and MnSOD activity. When cells pretreated with the cytokines were exposed to hyperoxia (95% O2, 72 h), menadione (5-50 microM, 4 h), or H2O2 (0.5 and 5 mM, 4 h), in all cases IFN-gamma and TNF-alpha enhanced oxidant-related cell injury. The effect was most significant with cells pretreated with a combination of IFN-gamma and TNF-alpha. Antioxidant enzymes such as total SOD, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase did not change significantly during the cytokine treatment. Catalase activity was not changed by IFN-gamma or TNF-alpha but it decreased significantly (34%) in IFN-gamma + TNF-alpha-treated cells. Free radical generation was not changed by these cytokines in acute (30 min) experimental conditions or after 48-h treatment. These results suggest that cytokine-induced MnSOD does not protect bronchial epithelial cells against endogenously or exogenously generated oxidants in vitro. In fact, cells that contained the highest MnSOD activity were the most sensitive to subsequent oxidant damage.
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PMID:Mitochondrial superoxide dismutase induction does not protect epithelial cells during oxidant exposure in vitro. 784 Feb 31

It is generally known that ischemic reperfusion injury is caused by cell membrane injuries due to superoxide. The present study was carried out to clarify an increase of superoxide production in human neutrophils in state of hypoxia and hyperoxia in vitro. Superoxide of neutrophils was studied at various PO2 values (air, 100% O2, 50% O2, and 100% N2 gas) by chemiluminescence method. The superoxide production (O2-) rates were 84% (air), 84% (100% N2), 87% (100% O2) and 84% (50% O2), respectively. At these stages, PO2 values were 178, 36, 764 and 370 mmHg, respectively. Since superoxide is generated in mitochondria under PO2 of 1 mmHg, it was considered that these different values of PO2 (100% N2, 100% O2 and 50% O2) do not influence the superoxide production. Other factors, such as PAF or cytokine, were speculated to increase superoxide production.
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PMID:[The changes in superoxide anion production in neutrophils on ischemia-reperfusion]. 796 22

Pulmonary oxygen toxicity is associated with histological evidence of polymorphonuclear neutrophil (PMN) infiltration into lung parenchyma. What guides infiltration of these cells is unknown. A number of chemoattractants for PMN have been documented including interleukin-8 (IL-8), a cytokine released by alveolar macrophages (AM) and other cell types. The purposes of this study were to 1) determine whether human AM and the histiocytic U937 cell line release IL-8 in response to hyperoxia, 2) assess whether hyperoxia results in increased IL-8 steady-state mRNA levels in U937 cells and 3) establish whether dexamethasone could attenuate noted effects of hyperoxia. Our study shows that hyperoxia stimulates human AM and U937 cell release of IL-8. Hyperoxia also increases IL-8 mRNA levels in U937 cells. IL-8 released in response to hyperoxia by AM was biologically active as evidenced by ability to induce PMN chemotaxis. A polyclonal antibody to IL-8 partially attenuated this chemotactic activity. Finally, dexamethasone at concentrations of 10 microM, 1 microM, and 100 nM markedly reduced hyperoxia-induced IL-8 release and mRNA synthesis by U937 cells. We conclude that IL-8 may be important in the pathogenesis of pulmonary oxygen toxicity and that therapeutic concentrations of dexamethasone can suppress production of this cytokine.
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PMID:Hyperoxia stimulates interleukin-8 release from alveolar macrophages and U937 cells: attenuation by dexamethasone. 807 42

Multiple insults may induce bronchopulmonary dysplasia (BPD) in premature infants, including the recently reported association of BPD with neonatal Ureaplasma urealyticum colonization. One mechanism of damage could involve stimulation of proinflammatory cytokine release from pulmonary fibroblasts. We therefore compared the effects of U. urealyticum, oxygen, and lipopolysaccharide (LPS) on the release of interleukin (IL)-1 beta, IL-6, and IL-8 from neonatal fibroblasts. Fibroblasts were grown in multiwell plates and divided into the following experimental conditions: fibroblasts alone, fibroblasts plus U. urealyticum (10,000 cfu/mL), and fibroblasts plus LPS (2 micrograms/mL). Plates were then exposed to room air or hyperoxia for 48 h, and supernatants were assayed for IL. U. urealyticum-infected fibroblasts produced a significant increase in IL-6 (P < .05) and a dramatic increase in IL-8 (P < .05) that was independent of hyperoxic exposure and significantly increased over that produced by LPS or hyperoxia alone. U. urealyticum is a potent inducer of fibroblast cytokine release in vitro and may contribute to the development of BPD.
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PMID:Induction of human neonatal pulmonary fibroblast cytokines by hyperoxia and Ureaplasma urealyticum. 839 7


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