Differential expression of pro-inflammatory and oxidative stress mediators induced by nitrogen dioxide and ozone in primary human bronchial epithelial cells

• Published in: Inhalation toxicology Vol. 28; no. 8; pp. 374 - 382
• Main Authors: Mirowsky, Jaime E., Dailey, Lisa A., Devlin, Robert B.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.07.2016
• Subjects: Adult; Air Pollutants - toxicity; Bronchi - cytology; Cells, Cultured; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Humans; In vitro; inflammation; nitrogen dioxide; Nitrogen Dioxide - toxicity; oxidant; oxidative stress; Oxidative Stress - drug effects; ozone; Ozone - toxicity; RNA, Messenger - metabolism; Transcriptome; nitrogen dioxide; oxidant; inflammation; In vitro; oxidative stress; ozone
• ISSN: 0895-8378; 1091-7691; 1091-7691
• DOI: 10.1080/08958378.2016.1185199

Context: NO 2 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 NO 2 and O 3 induce toxicity by activating similar cellular pathways. Methods: Primary human bronchial epithelial cells (HBECs, n = 3 donors) were exposed for 2 h at an air-liquid interface to 3 ppm NO 2 , 0.75 ppm O 3 , or filtered air and harvested 1 h 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 NO 2 (1, 2, 3, or 5 ppm), O 3 (0.25, 0.50, 0.75, or 1.00 ppm), or filtered air and harvesting 0, 1, 4 and 24 h post-exposure. Results: Using the arrays, genes related to oxidative stress were highly induced with NO 2 while expression of pro-inflammatory and vascular function genes was found subsequent to O 3 . NO 2 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 1 h post-exposure and NO 2 produced a maximal response after 4 h. Conclusion: We have demonstrated that these two oxidant gases stimulate differing mechanistic responses in vitro and these responses occur at dissimilar times.