Ozone-dependent increases in lung glucocorticoids and macrophage response: Effect modification by innate stress axis function
- DOI
- Language of the publication
- English
- Date
- 2021-04-18
- Type
- Article
- Author(s)
- Thomas, Jith
- Stalker, Andrew
- Breznan, Dalibor
- Thomson, Errol M.
- Publisher
- Elsevier
Abstract
Although considerable inter-individual variability exists in health effects associated with air pollutant exposure, underlying reasons remain unclear. We examined whether innate differences in stress axis function modify lung glucocorticoid and macrophage responses to ozone (O3). Highly-stress responsive Fischer (F344) and less responsive Lewis (LEW) rats were exposed for 4 h by nose-only inhalation to air or O3 (0.8 ppm). Ozone increased corticosterone recovered by bronchoalveolar lavage in both strains (F344 > LEW). Higher corticosterone in F344 was associated with a blunted response to O3 of macrophage pro-inflammatory genes compared to LEW. Pharmacological inhibition of O3-dependent corticosterone production in F344 enhanced the inflammatory gene response to O3, mimicking the LEW phenotype. Examination of potential impacts of glucocorticoids on macrophage function using a human monocyte-derived macrophage cell line (THP-1) showed that cortisol modified phagocytosis in a macrophage phenotype-dependent manner. Overall, our data implicate endogenous glucocorticoids in the regulation of pulmonary macrophage responses to O3.
Plain language summary
Health Canada is responsible for assessing risks posed by air pollutants. Exposure to ozone, a common air pollutant, is linked to respiratory morbidity and mortality. While this highly reactive gas can injure the lungs directly, vulnerability may be determined by factors that vary from one person to another. Stress hormones called glucocorticoids that circulate in our blood play critical roles in regulating immune and inflammatory responses; however the role of glucocorticoids in mediating or modifying effects of ozone on lung immune cells has not been studied. Health Canada scientists sought to determine whether innate differences in glucocorticoid levels alter inflammatory responses in lung immune cells (macrophages) collected from ozone-exposed rats. They also tested the role of glucocorticoids in modifying macrophage function using human cells. They found that ozone increased glucocorticoids in the blood and lungs, and that higher levels were associated with a blunted inflammatory response in macrophages. Glucocorticoids also altered the capacity of macrophages to engulf particles, a critical function in protecting the lungs. The study demonstrated that the level of stress hormone is an important determining factor in regulating lung macrophage function and their response to ozone. The study provides new insight into factors underlying susceptibility to air pollution, in support of Health Canada programs intended to protect health from the adverse effects of air pollutants.
Subject
- Health,
- Health and safety