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)

Keratinocyte growth factor (KGF) has recently been shown to protect rats from hyperoxia-induced lung injury. However, the mechanism of the protective effect of KGF remains unclear. To elucidate the mechanism of action of KGF, we determined the effect of KGF on the barrier function of epithelial monolayers exposed to H(2)O(2). Calu-3 (human airway epithelial cells) were grown on Transwell membranes, and the permeability to fluorescein isothiocyanate-albumin was measured. Exposure to 0.5 mM H(2)O(2) significantly increased permeability from 1.50 +/- 0.09 to 24.8 +/- 1.5 (mean +/- SE x 10(-6) cm/s; P < 0.001). Incubation of monolayers with 50 ng/ml KGF for 24 h significantly reduced basal albumin flux (0.85 +/- 0.09; P < 0.001), and pretreatment with KGF completely abolished the H(2)O(2)-induced permeability increase (1.08 +/- 0.09). The protective effect of KGF was dose dependent and was observed at concentrations as low as 1 ng/ml. Partial amelioration of the H(2)O(2)-induced permeability increase occurred after 1 h of exposure to KGF. Treatment of cells with calphostin C, an inhibitor of protein kinase C (PKC), had no effect on the permeability of control or H(2)O(2)-treated cells. Calphostin C abolished both the KGF-mediated decrease in basal albumin flux and the protective effect of KGF against H(2)O(2)-induced increases in permeability. KGF pretreatment also prevented H(2)O(2)-induced disruption of F-actin staining patterns, suggesting stabilization of the cytoskeleton. These studies demonstrate that KGF decreases albumin flux across airway epithelial monolayers and prevents H(2)O(2)-induced increases in permeability by a PKC-dependent process that may involve stabilization of the cytoskeleton.
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PMID:KGF prevents hydrogen peroxide-induced increases in airway epithelial cell permeability. 914 42

Exogenous surfactant is critical in the treatment of neonates with respiratory distress syndrome. Lucinactant (Surfaxin; Discovery Laboratories, Inc.) is a surfactant replacement therapy containing sinulpeptide, which may reduce lung inflammation. This study tested whether Lucinactant reduces markers of inflammation, damage and remodeling in human airway epithelial cells exposed to hyperoxia. Calu-3 monolayers cultured at an air-liquid interface were treated apically with 140 microL of normal saline, Lucinactant or Beractant (Survanta; Abbott Laboratories, Inc.). Treated monolayers were exposed to 60% O(2)/5% CO(2) for 24 or 72 h. Transepithelial resistance (TER; p < 0.001) and cell viability (p < 0.05) were greater in both surfactant groups compared with saline; by 72 h Lucinactant cells had greater TER than Beractant (p < 0.001). Surfactant treated groups secreted less IL-8 than saline (p < 0.001), whereas Lucinactant cells secreted less IL-6 than saline and Beractant (p < 0.001). Matrix metalloproteinase 7, expressed by saline and Beractant treated cells at 24 h, was attenuated by 72 h by Beractant (p < 0.001), but was never detected in Lucinactant cells. Histology indicated less injury with Lucinactant relative to Beractant and saline. These data suggest that Lucinactant was protective compared with Beractant and control.
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PMID:KL4-surfactant (Lucinactant) protects human airway epithelium from hyperoxia. 1839 44

We tested the hypothesis that hyperoxia or pressure exposure differentially activates expression of cytokines and/or matrix modeling proteins in human airway epithelial cells. Calu-3 epithelial cell monolayers were cultured on transwell plates with the apical surface exposed to gas. Following establishment of baseline, plates were placed in a chamber and exposed to: control (21% O (2); atm), hyperoxia (60% O (2); atm), pressure (21% O (2); 40 cm H (2)O), and combination (60% O (2); 40 cm H (2)O). At 72 hour of exposure, monolayers were assessed for integrity, viability, and expression of interleukin (IL)-6, IL-8 and matrix metalloproteinases (MMPs) -2, -7, and -9. Compared with controls, hyperoxia had lower transepithelial resistance ( P < 0.001) and greater IL-6 secretion ( P < 0.01), and pressure had lower cell viability ( P < 0.001) and greater IL-8 secretion ( P < 0.001). Hyperoxia resulted in more latent MMP-2 ( P < 0.05) and MMP-7 ( P < 0.001). Pressure was associated with a rise in MMPs independent of oxygen exposure ( P < 0.05). Hyperoxia and pressure differentially affected MMP activities in Calu-3 cells and may lead to the different functional and structural abnormalities observed in these in vitro studies.
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PMID:Dissociation between the effects of oxygen and pressure on matrix metalloproteinase-2, -7, and -9 expression in human airway epithelial cells. 1872 Mar 22

This article reviews the application of the human airway Calu-3 cell line as a respiratory model for studying the effects of gas concentrations, exposure time, biophysical stress, and biological agents on human airway epithelial cells. Calu-3 cells are grown to confluence at an air-liquid interface on permeable supports. To model human respiratory conditions and treatment modalities, monolayers are placed in an environmental chamber, and exposed to specific levels of oxygen or other therapeutic modalities such as positive pressure and medications to assess the effect of interventions on inflammatory mediators, immunologic proteins, and antibacterial outcomes. Monolayer integrity and permeability and cell histology and viability also measure cellular response to therapeutic interventions. Calu-3 cells exposed to graded oxygen concentrations demonstrate cell dysfunction and inflammation in a dose-dependent manner. Modeling positive airway pressure reveals that pressure may exert a greater injurious effect and cytokine response than oxygen. In experiments with pharmacological agents, Lucinactant is protective of Calu-3 cells compared with Beractant and control, and perfluorocarbons also protect against hyperoxia-induced airway epithelial cell injury. The Calu-3 cell preparation is a sensitive and efficient preclinical model to study human respiratory processes and diseases related to oxygen- and ventilator-induced lung injury.
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PMID:Cultured human airway epithelial cells (calu-3): a model of human respiratory function, structure, and inflammatory responses. 2094 83