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

Abstract

Ozone (O), a ubiquitous urban air pollutant, causes adverse pulmonary and extrapulmonary effects. A large variability in acute O-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 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-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, and euthanized immediately after exposure. As expected, baseline (air-exposed) plasma corticosterone was significantly lower in the hypo-stress responsive LEW. Although O exposure increased plasma corticosterone in both strains, corticosterone remained significantly lower in LEW when compared to F334. LEW exhibited greater O-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 compared with LEW, they had greater levels of lung injury biomarkers. Our results indicate that stress axis variability is associated with differential O-induced lung toxicity. Given the large variability in stress axis reactivity among humans, stress axis regulation could potentially be a determining factor underlying O sensitivity.

Exposure to air pollutants and the gut microbiota: a potential link between exposure, obesity, and type 2 diabetes

“…[45][46][47][48] Additionally, ozone-induced activation of the sympathetic nervous system may result in the release of hormones. 49,50 Each of these pathways may result in gut microbiome facilitated biotransformations, 51,52 changes in gut bacterial diversity, 25 alterations in the relative abundance of gut bacterial taxa, 24,25,83 tight junction disruption, 40 and activation of immune cells and adrenergic neurons. 26,50,53,54 traffic-related air pollution, 61 has also been shown to alter the composition of the gut microbiota in human [62][63][64] and animal studies.…”

Air Pollution, Stress, and Allostatic Load: Linking Systemic and Central Nervous System Impacts

“…Intrinsic factors such as age, sex, gender, stress reactivity, and existing disease, and extrinsic factors such as co-exposure to psychosocial and other stressors, may all potentially contribute to individual responses to pollutants. In rodent models, interstrain differences in stress axis function are associated with differences in lung injury and inflammatory response following exposure to ozone [151], suggesting that such variability may be relevant to susceptibility to pollutants. It will be important to assess to what extent interindividual differences are related to susceptibility to CNS impacts of air pollutants.…”

Exposure to Diesel Exhaust and Plasma Cortisol Response: A Randomized Double-Blind Crossover Study

“…037701-2 129(3) March 2021 relation to individual characteristics may have relevance to individual risk of local and systemic health effects of air pollutants (Thomas et al 2018;Thomson 2019).…”