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Ozone-dependent increases in lung glucocorticoids and macrophage response: Effect modification by innate stress axis
Jith Thomas1, Andrew Stalker2, Dalibor Breznan1
1Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, K1A 0K9, Canada.
Environmental Toxicology and Pharmacology
|April 20, 2021
Summary
Individual stress responses influence lung inflammation from ozone (O3) exposure. Higher stress hormones in some rats blunted O3-induced inflammatory genes, suggesting glucocorticoids regulate macrophage responses to air pollutants.
Area of Science:
- Environmental Health
- Immunology
- Endocrinology
Background:
- Inter-individual variability in air pollutant health effects is significant but poorly understood.
- The role of the stress axis and glucocorticoids in modulating lung responses to ozone (O3) is unclear.
Purpose of the Study:
- To investigate if innate differences in stress axis function affect lung glucocorticoid and macrophage responses to O3 exposure.
- To determine the impact of endogenous glucocorticoids on pulmonary macrophage inflammatory gene expression and function.
Main Methods:
- Exposure of Fischer (F344) and Lewis (LEW) rats, differing in stress responsiveness, to air or O3 (0.8 ppm) via nose-only inhalation.
- Measurement of corticosterone in bronchoalveolar lavage fluid.
- Analysis of macrophage pro-inflammatory gene expression.
- Pharmacological inhibition of O3-induced corticosterone production in F344 rats.
- In vitro assessment of cortisol effects on human monocyte-derived macrophage (THP-1) phagocytosis.
Main Results:
- Ozone exposure increased corticosterone levels in bronchoalveolar lavage fluid in both rat strains, with higher levels in F344 rats compared to LEW rats.
- Higher endogenous corticosterone in F344 rats was associated with a blunted O3-induced inflammatory gene response in macrophages compared to LEW rats.
- Inhibiting O3-dependent corticosterone production in F344 rats enhanced their inflammatory gene response to O3, mimicking the LEW phenotype.
- Cortisol modulated phagocytosis in human THP-1 cells in a manner dependent on macrophage phenotype.
Conclusions:
- Endogenous glucocorticoids play a critical role in regulating pulmonary macrophage responses to ozone exposure.
- Innate differences in stress axis function can significantly influence the inflammatory response to air pollutants.
- Glucocorticoid levels may explain some of the inter-individual variability observed in air pollution-related health effects.
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