Administration of supplemental oxygen is frequently encountered in infants suffering from pulmonary insufficiency and in adults with acute respiratory distress syndrome. However, hyperoxia causes acute lung damage in experimental animals. In the present study, we investigated the roles of the Ah receptor (AHR) in the modulation of cytochrome P4501A (CYP1A) enzymes and in the development of lung...

The direct effects of hyperoxia on collagen production by fetal lung fibroblasts are unknown and would be important to the understanding of the molecular mechanisms involved in bronchopulmonary dysplasia in premature infants. We studied the effect of hyperoxia on 1) proliferation, 2) mRNA levels for type I and III procollagens, and 3) net collagen production in primary cultures of fetal rat lun...

Ectothermic animals living at high elevation often face interacting challenges, including temperature extremes, intense radiation, and hypoxia. While high-elevation specialists have developed strategies to withstand these constraints, the factors preventing downslope migration are not always well understood. As mean temperatures continue rise climate patterns become more extreme, such transloca...

OBJECTIVE Corticosteroids and hyperoxia protect the heart against ischemia-reperfusion injury and may attenuate vascular reactivity. We hypothesized that (1) combining these two pretreatments induces an additive cardioprotection, (2) protection depends on activation of survival kinases and/or heat shock proteins, and (3) these interventions would change vascular reactivity into a more relaxed s...

Previous studies have demonstrated that hyperoxia-induced stress and oxidative damage to the lungs of mice lead to an increase in IL-6, TNF-α, and TGF-β expression. Together, IL-6 and TGF-β have been known to direct T cell differentiation toward the TH17 phenotype. In the current study, we tested the hypothesis that hyperoxia promotes the polarization of T cells to the TH17 cell phenotype in re...

RATIONALE Human data suggest that the incidence of acute lung injury is reduced in patients with type II diabetes mellitus. However, the mechanisms by which diabetes confers protection from lung injury are unknown. OBJECTIVES To determine whether leptin resistance, which is seen in humans with diabetes, protects mice from hyperoxic lung injury. METHODS Wild-type (leptin responsive) and db/d...

Alveolar epithelial apoptosis is an important feature of hyperoxia-induced lung injury in vivo and has been described in the early stages of bronchopulmonary dysplasia (chronic lung disease of preterm newborn). Molecular regulation of hyperoxia-induced alveolar epithelial cell death remains incompletely understood. In view of functional involvement of Fas/FasL system in physiological postcanali...

Lung epithelial cell apoptosis is an important feature of hyperoxia-induced lung injury. Death receptor-associated extrinsic pathway and mitochondria-associated intrinsic pathway both mediate the development of lung epithelial cell apoptosis. Despite decades of research, molecular mechanisms of hyperoxia-induced epithelial cell apoptosis remain incompletely understood. Here we report a novel re...

PURPOSE To investigate whether the absence of the Fas-Fas ligand system of apoptosis regulation affects hyperoxia-induced retinal vaso-obliteration and retinal neovascularization in a mouse model of oxygen-induced retinopathy. METHODS C57BL/6 (B6) and congenic Fas ligand-deficient generalized lymphoproliferative disease (gld) mice were exposed to 75% oxygen from postnatal day (P)7 to P12 and ...

Many preterm infants require hyperoxic gas for survival, although it can contribute to lung injury. Experimentally, neonatal hyperoxia leads to persistent alterations in lung structure and increases leukocytes in bronchoalveolar lavage fluid (BALF). These effects of hyperoxia on the lungs are considered to be caused, at least in part, by increased oxidative stress. Our objective was to determin...