Journal
INHALATION TOXICOLOGY
Volume 28, Issue 8, Pages 374-382Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/08958378.2016.1185199
Keywords
In vitro; inflammation; nitrogen dioxide; oxidant; oxidative stress; ozone
Categories
Funding
- United States Environmental Protection Agency
- EPA Cooperative Agreement with the Center for Environmental Medicine, Asthma, and Lung Biology at the University of North Carolina [CR83346301]
- National Institutes of Environmental Health Sciences [T32ES007126]
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Context: NO2 and O-3 are ubiquitous air toxicants capable of inducing lung damage to the respiratory epithelium. Due to their oxidizing capabilities, these pollutants have been proposed to target specific biological pathways, but few publications have compared the pathways activated.Objective: This work will test the premise that NO2 and O-3 induce toxicity by activating similar cellular pathways.Methods: Primary human bronchial epithelial cells (HBECs, n=3 donors) were exposed for 2h at an air-liquid interface to 3ppm NO2, 0.75ppm O-3, or filtered air and harvested 1h post-exposure. To give an overview of pathways that may be influenced by each exposure, gene expression was measured using PCR arrays for toxicity and oxidative stress. Based on the results, genes were selected to quantify whether expression changes were changed in a dose- and time-response manner using NO2 (1, 2, 3, or 5ppm), O-3 (0.25, 0.50, 0.75, or 1.00ppm), or filtered air and harvesting 0, 1, 4 and 24h post-exposure.Results: Using the arrays, genes related to oxidative stress were highly induced with NO2 while expression of pro-inflammatory and vascular function genes was found subsequent to O-3. NO2 elicited the greatest HMOX1 response, whereas O-3 more greatly induced IL-6, IL-8 and PTGS2 expression. Additionally, O-3 elicited a greater response 1h post-exposure and NO2 produced a maximal response after 4h.Conclusion: We have demonstrated that these two oxidant gases stimulate differing mechanistic responses in vitro and these responses occur at dissimilar times.
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