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Differential Expression of pro-inflammatory and oxidative stress mediators induced by nitrogen dioxide and ozone in primary human bronchial epithelial cells
Mirowsky, J., L. Dailey, AND R. Devlin. Differential Expression of pro-inflammatory and oxidative stress mediators induced by nitrogen dioxide and ozone in primary human bronchial epithelial cells. INHALATION TOXICOLOGY. Taylor & Francis, Inc., Philadelphia, PA, 28(8):374-82, (2016).
OAR has listed as a high priority a better understanding of the mode of action by which different air pollutants cause adverse health effects. This paper shows that NO2 and O3 activates different pathophysiological pathways, with O3 activating pro-inflammatory pathways and NO2 activating oxidative stress pathways.
CONTEXT: N02 and 03 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 N02 and 03 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 N02, 0.75 ppm 03, 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 N02 (1, 2, 3, or 5 ppm), 03 (0.25, 0.50, 0.75, or 1.00ppm), orfiltered air and harvesting 0, 1,4 and 24 h post-exposure.RESULTS: Using the arrays, genes related to oxidative stress were highly induced with N02 while expression of pro-inflammatory and vascular function genes was found subsequent to 03. N02 elicited the greatest HMOX1 response, whereas 03 more greatly induced IL-6, IL-8 and PTGS2 expression. Additionally, 03 elicited a greater response 1 h post-exposure and N02 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.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
ENVIRONMENTAL PUBLIC HEALTH DIVISION