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Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injury
Citation:
Henriquez, A., S. Snow, D. Miller, AND U. Kodavanti. Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injury. Presented at Keystone Symposia on Molecular and Cellular Biology: Autophagy (E6), Breckenridge, CO, June 19 - 24, 2015.
Impact/Purpose:
The contribution of autophagy in orchestrating biological events after pollutant exposure is not well characterized. The potential for intervening this process might inform preventive strategies. Our data demonstrate that exposure to air pollutants in vivo and in vitro is associated with changes in autophagy endpoints, which is influenced by the underlying disease and the pollutant type.
Description:
Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injuryHenriquez, A.1, Snow, S.2, Miller, D1.,Schladweiler, M.2 and Kodavanti, U2.1 Curriculum in Toxicology, UNC, Chapel Hill, NC. 2 EPHD/NHEERL, US EPA, RTP, Durham, NC. Air pollution is linked to chronic respiratory disease and blamed for ~7 million premature deaths annually worldwide. Inhaled pollutants induce lung injury and inflammation. These responses are exacerbated in individuals with underlying chronic conditions such as diabetes and cardiovascular disease. The contribution of autophagy in orchestrating these events after pollutant exposure is not well characterized. The potential for intervening this process might inform preventive strategies. To evaluate the link between air pollution and autophagy, we quantified LC3II protein levels and the expression of autophagy-related gene targets in the lung extracts of Wistar Kyoto rats exposed to major anthropogenic components of pollution (nickel, asbestos, diesel exhaust and ozone [O3]) and respective controls. We also examined these markers following an acute air or O3 exposure in the lungs of healthy Wistar and Goto Kakizaki (GK) rats with type II diabetes. Our results indicate that LC3II is increased after exposure to nickel and asbestos but not diesel exhaust or O3 in healthy rats. This is associated with transcriptional increases in a number of autophagy markers in the lung. Lc3a, Lc3b and Atg5 mRNA expressions are increased significantly after O3 exposure but only in the lungs of the diabetic GK rats. Importantly, the O3-induced lung injury and cytokine gene expression are exacerbated in these rats relative to healthy rats. To investigate potential mechanisms by which air pollutants modulate toxic responses through autophagy, we developed an in vitro human bronchial epithelial cell model expressing GFP-LC3. Our data demonstrate that exposure to air pollutants in vivo and in vitro is associated with changes in autophagy endpoints, which is influenced by the underlying disease and the pollutant type. Supported by Fulbright (CONICYT) and EPA-UNC Co-operative Agreement with Curriculum in Toxicology and CEMALB.