Modulation by Ozone of Glucocorticoid-Regulating Factors in the Lungs in Relation to Stress Axis Reactivity
- DOI
- Language of the publication
- English
- Date
- 2021-11-03
- Type
- Article
- Author(s)
- Thomas, Jith
- Thomson, Errol M.
- Publisher
- MDPI
Abstract
Exposure to air pollutants increases levels of circulating glucocorticoid stress hormones that exert profound effects relevant to health and disease. However, the nature and magnitude of tissue-level effects are modulated by factors that regulate local glucocorticoid activity; accordingly, inter-individual differences could contribute to susceptibility. In the present study, we characterized effects of ozone (O3) inhalation on glucocorticoid-regulating factors in the lungs of rat strains with contrasting hypothalamic–pituitary–adrenal stress axis responses. Hyper-responsive Fischer (F344) and less responsive Lewis (LEW) rats were exposed to air or 0.8 ppm O3 for 4 h by nose-only inhalation. Levels of the high-specificity and -affinity corticosteroid-binding globulin protein increased in the lungs of both strains proportional to the rise in corticosterone levels following O3 exposure. Ozone reduced the ratio of 11β-hydroxysteroid dehydrogenase type 1 (HSDB1)/HSDB2 mRNA in the lungs of F344 but not LEW, indicating strain-specific transcriptional regulation of the major glucocorticoid metabolism factors that control tissue-level action. Intercellular adhesion molecule (ICAM)-1 and total elastase activity were increased by O3 in both strains, consistent with extravasation and tissue remodeling processes following injury. However, mRNA levels of inflammatory markers were significantly higher in the lungs of O3-exposed LEW compared to F344. The data show that strain differences in the glucocorticoid response to O3 are accompanied by corresponding changes in regulatory factors, and that these effects are collectively associated with a differential inflammatory response to O3. Innate differences in glucocorticoid regulatory factors may modulate the pulmonary effects of inhaled pollutants, thereby contributing to differential susceptibility.
Plain language summary
Health Canada conducts research to support risk assessment and mitigation of health impacts of air pollutants. Health Canada research in this area has established that exposure to air pollution increases the production of stress hormones that, when chronically elevated, can adversely affect our health and also that differences in our body's stress response system may underlie differences in sensitivity to air pollutants. In the present study, Health Canada researchers examined how breathing air pollution may change how our lungs react to stress hormones called glucocorticoids. They conducted a study in which rat strains that differed according to how they respond to stress - highly-stress reactive vs. low-stress reactivity - were exposed to the common pollutant ozone. They found that ozone changed the levels of proteins and genes that are important in controlling to what extent glucocorticoids exert effects in the lungs. These effects differed by rat strain, and were associated with differences in the inflammatory response to ozone. The results provide further support for the idea that individual differences in our stress response systems may contribute to susceptibility to the adverse effects of air pollutants.
Subject
- Health,
- Health and safety