Stress axis variability is associated with differential ozone-induced lung inflammatory signaling and injury biomarker response
Highlights: • Fischer and Lewis rats exhibited distinct stress axis responses to ozone inhalation. • Hypo-stress responsive Lewis rats had a greater lung inflammatory response. • Hyper-stress responsive Fischer rats had a greater lung injury response. • Innate stress axis differences may play a role in ozone-induced lung toxicity. Ozone (O{sub 3}), a ubiquitous urban air pollutant, causes adverse pulmonary and extrapulmonary effects. A large variability in acute O{sub 3}-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 O{sub 3} 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 O{sub 3}-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 O{sub 3}, and euthanized immediately after exposure. As expected, baseline (air-exposed) plasma corticosterone was significantly lower in the hypo-stress responsive LEW. Although O{sub 3} exposure increased plasma corticosterone in both strains, corticosterone remained significantly lower in LEW when compared to F334. LEW exhibited greater O{sub 3}-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 O{sub 3} compared with LEW, they had greater levels of lung injury biomarkers. Our results indicate that stress axis variability is associated with differential O{sub 3}-induced lung toxicity. Given the large variability in stress axis reactivity among humans, stress axis regulation could potentially be a determining factor underlying O{sub 3} sensitivity.
- OSTI ID:
- 23095608
- Journal Information:
- Environmental Research, Vol. 167; Other Information: Crown Copyright Copyright (c) 2018 Published by Elsevier Inc.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0013-9351
- Country of Publication:
- United States
- Language:
- English
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