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• W2891411499 abstract "Ozone (O3), a ubiquitous urban air pollutant, causes adverse pulmonary and extrapulmonary effects. A large variability in acute O3-induced effects has been observed; however, the basis for interindividual differences in susceptibility is unclear. We previously demonstrated a role for the hypothalamic-pituitary-adrenal (HPA) stress axis and glucocorticoid response in acute O3 toxicity. Glucocorticoids have important anti-inflammatory actions, and have been shown to regulate lung inflammatory responses. We hypothesised that a hyporesponsive HPA axis would be associated with greater O3-dependent lung inflammatory signaling. Two genetically-related rat strains with known differences in stress axis reactivity, highly-stress responsive Fischer (F344) and less responsive Lewis (LEW), were exposed for 4 h by nose-only inhalation to clean air or 0.8 ppm O3, and euthanized immediately after exposure. As expected, baseline (air-exposed) plasma corticosterone was significantly lower in the hypo-stress responsive LEW. Although O3 exposure increased plasma corticosterone in both strains, corticosterone remained significantly lower in LEW when compared to F334. LEW exhibited greater O3-induced inflammatory cytokine/chemokine signaling compared to F344, consistent with the lower corticosterone levels. Since we observed strain-specific differences in inflammatory signaling, we further investigated injury biomarkers (total protein, albumin and lactate dehydrogenase). Although the hyper-responsive F344 exhibited lower inflammatory signaling in response to O3 compared with LEW, they had greater levels of lung injury biomarkers. Our results indicate that stress axis variability is associated with differential O3-induced lung toxicity. Given the large variability in stress axis reactivity among humans, stress axis regulation could potentially be a determining factor underlying O3 sensitivity." @default.
• W2891411499 created "2018-09-27" @default.
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• W2891411499 date "2018-11-01" @default.
• W2891411499 modified "2023-09-24" @default.
• W2891411499 title "Stress axis variability is associated with differential ozone-induced lung inflammatory signaling and injury biomarker response" @default.
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• W2891411499 doi "https://doi.org/10.1016/j.envres.2018.09.007" @default.
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