Stress axis variability is associated with differential ozone-induced lung inflammatory signaling and injury biomarker response

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DOI

https://doi.org/10.1016/j.envres.2018.09.007

Language of the publication
English
Date
2018-09-08
Type
Article
Author(s)
  • Thomas, Jith
  • Guénette, Josée
  • Thomson, Errol M.
Publisher
Elsevier

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.

Plain language summary

Ozone, a common air pollutant in urban areas, has been shown to cause lung inflammation and injury, increase hospital admission rates, and contribute to premature death. Some people are more vulnerable to ozone than others. While the exact mechanisms governing susceptibility to ozone are not well understood, recent Health Canada studies have shown that exposure to air pollutants increases the release of stress hormones (cortisol in humans, corticosterone in rodents). Health Canada conducted a study to assess whether differences in stress response could modify effects of ozone on the lungs. Two genetically related rat strains with known differences in their stress response, highly stress-responsive Fischer and less responsive Lewis, were exposed to air or ozone. As expected, blood levels of corticosterone were significantly lower in the Lewis rats, and this was associated with greater lung inflammation, but lower markers of injury. Given the large variability in stress function among humans, the results suggest a possible factor underlying sensitivity to ozone, and contribute to our understanding of health effects of air pollution in the human population.

Subject

  • Health,
  • Health and safety

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Healthy environments, consumer safety and consumer products

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