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Characterization of Impacts of the Interactions Between Concentrated Ambient Particles and Ozone on Protein and Toxicity Responses in Rat Lung and Aorta Tissues
Citation:
Bruno, M., Y. Ge, AND A. Farraj. Characterization of Impacts of the Interactions Between Concentrated Ambient Particles and Ozone on Protein and Toxicity Responses in Rat Lung and Aorta Tissues. Society of Toxicology, RTP, NC, March 15 - 19, 2020.
Impact/Purpose:
Very little is known about the similarities and differences in mechanisms underlying the effects of single versus multi-pollutant exposures. By characterizing these differences and their role in exposure-associated adverse effects, both in vitro and in vivo, we will have a better ability to predict both exposure outcomes and susceptible populations.
Description:
Characterization of Impacts of the Interactions Between Concentrated Ambient Particles and Ozone on Protein and Toxicity Responses in Rat Lung and Aorta Tissues Particulate matter (PM) and ozone (O3) are major components of air pollution. There has been substantial improvement in our understanding of the toxicity pathways and biological mechanisms involved in PM or O3-mediated adverse pulmonary and cardiovascular effects. PM and O3 can have independent and potentially synergistic or antagonistic effects. One postulated mechanism for the elicitation of cardiovascular responses in response to air pollution inhalation is the triggering of pulmonary inflammation that then “spills-over” into the circulation causing vascular inflammation and injury. However, little is known about the effects of the interactions between PM and O3 in a co-exposure context on protein and toxicity responses in pulmonary and cardiovascular tissue. The present study was undertaken to characterize proteomic and toxicity impacts in lung and aortic tissues of spontaneously hypertensive rats exposed to concentrated ambient particulate (CAP) matter and O3, singly or in combination. Rats were exposed once for 4 hours by whole-body inhalation to fine CAPs alone (target concentration: 150 g/m3), O3 (0.2 ppm) alone, CAPs plus O3, or filtered air during summer 2011 and winter 2012. Changes in expression and/or phosphorylation levels of protein biomarkers of respiratory and cardiovascular disease, and key regulators of toxicity pathways involving cell proliferation and differentiation, apoptosis, oxidative stress, and inflammation were assessed. It was found that PM increased interlukin-6 and RAGE protein expression in lung tissue and eotaxin-1 expression in aortic tissue, whereas O3 increased expression of CCL11, interleukin-1 receptor antagonist (IL-1RA), and IL-2RA in lung tissue and intelukin-10 (IL-10) in aortic tissue. By contrast, co-exposure to PM and O3 altered expression of CCL5, brain-derived neurotrophic factor (BDNF), and hepatocyte growth factor (HGF). Multivariate statistical analysis and mathematical modeling of PM and O3-mediated protein responses was performed to identify correlations between protein expression/phosphorylation and toxicity responses to PM, O3, and their combination. Our results demonstrate that the tissue-dependent variability in proteomic responses or proteome changes is related to the different components of the mixture, and the types of pathway initiated. (The information in this Abstract has been funded wholly by the U. S. Environmental Protection Agency. It has been subjected to review by the Center for Computational Toxicology and Exposure and approved for presentation. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.)