Mapping Acute Systemic Effects of Inhaled Particulate Matter and Ozone: Multiorgan Gene Expression and Glucocorticoid Activity

Abstract

Recent epidemiological studies have demonstrated associations between air pollution and adverse effects that extend beyond respiratory and cardiovascular disease, including low birth weight, appendicitis, stroke, and neurological/neurobehavioural outcomes (e.g., neurodegenerative disease, cognitive decline, depression, and suicide). To gain insight into mechanisms underlying such effects, we mapped gene profiles in the lungs, heart, liver, kidney, spleen, cerebral hemisphere, and pituitary of male Fischer-344 rats immediately and 24h after a 4-h exposure by inhalation to particulate matter (0, 5, and 50mg/m3 EHC-93 urban particles) and ozone (0, 0.4, and 0.8 ppm). Pollutant exposure provoked differential expression of genes involved in a number of pathways, including antioxidant response, xenobiotic metabolism, inflammatory signalling, and endothelial dysfunction. The mRNA profiles, while exhibiting some interorgan and pollutant-specific differences, were remarkably similar across organs for a set of genes, including increased expression of redox/glucocorticoid-sensitive genes and decreased expression of inflammatory genes, suggesting a possible hormonal effect. Pollutant exposure increased plasma levels of adrenocorticotropic hormone and the glucocorticoid corticosterone, confirming activation of the hypothalamic-pituitary-adrenal axis, and there was a corresponding increase in markers of glucocorticoid activity. Although effects were transient and presumably represent an adaptive response to acute exposure in these healthy animals, chronic activation and inappropriate regulation of the hypothalamic-pituitary-adrenal axis are associated with adverse neurobehavioral, metabolic, immune, developmental, and cardiovascular effects. The experimental data are consistent with epidemiological associations of air pollutants with extrapulmonary health outcomes and suggest a mechanism through which such health effects may be induced.

Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

“…Both leptin and epinephrine changes are associated with a reversible decrease in body temperature (23), suggesting involvement of the sympathetic axis and changes in hypothalamic thermoregulation. Increased corticotropin and cortisol levels after ozone exposure have also been noted in other rodent studies (21,32). In this study, humans exposed to ozone also presented elevated circulating cortisol and corticosterone, suggesting the activation of the HPA axis, similar to rats.…”

“…Specifically, exposure to ozone activates the nucleus tractus solitarius and stress responsive regions of the hypothalamus through stimulation of pulmonary vagal C fibers (18). Acute ozone exposure can increase levels of circulating stress hormones, such as epinephrine and corticosterone, in rats (19)(20)(21). Ozone exposure also induces cardiac autonomic effects in humans (22); hypothermia and bradycardia in rats (23); and leptinemia, hyperglycemia, glucose intolerance, and global changes in circulating metabolites involved in peripheral glucose, lipid, and amino acid metabolism in rats (20).…”

Particulate Matter Air Pollution and the Risk of Incident CKD and Progression to ESRD

“…35 Evidence suggests that increased PM 2.5 concentrations are associated with significant decrease in flow-mediated dilatation, 36,37 increases in systolic BP and pulse pressure, [38][39][40] and disturbances in the hypothalamic-pituitary-adrenal axis. 41 Emerging evidence also suggests that exposure to ambient air pollutants can lead to metabolic disturbances, including glucose intolerance, decreased insulin sensitivity, higher blood lipid concentrations, weight gain, and increased risk of diabetes mellitus. [42][43][44] It is plausible that one or more of these mechanistic pathways may explain the association described here.…”

The Maternal Thyroid Gland as A Sentinel Organ for A Development: Signs of The Possible Harm of Air Pollution in Development

“…reported that exposure women to airborne PM2.5 during pregnancy can disrupt the activities of free T4, free T3 and thyroidstimulating-hormone (TSH) and contribute to decrease the birth weight. Moreover, PM exposure in rats can perturb the action of hypothalamic-pituitary-thyroid axis (HPTA) (Thomson et al 2013). Exposure pregnant to urbane air might induce premature deaths (Cohen et al, 2017).…”

“…Exposure pregnant to urbane air might induce premature deaths (Cohen et al, 2017). These variations may be attributed to PM exposure during the gestation can increase the activity of glucocorticoid (Thomson et al 2013) suppressing the release of TSH (Wilber and Utiger 1969). Also, the antiinflammatory actions of glucocorticoids can induce the response of a systemic oxidative stress (Janssen et al 2012) and elevate the placental protein-bound 3-nitrotyrosine (Saenen et al 2016).…”