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Scavenger receptor BI regulates oxidized lipid driven pulmonary and vascular inflammation after ozone exposure

Principal Investigator: 
,

East Carolina University

This New Investigator Award study is evaluating whether injury after exposure to ozone is mediated through changes in the lung and blood of levels of oxidized phospholipids. This will be tested in normal mice and in mice genetically lacking the Scavenger Receptor B1 that binds oxidized phospholipids.

Funded under
Status: 
Ongoing
Abstract
Abstract for the 2019 HEI Annual Conference
 

Dietary DHA mitigates ozone induced pulmonary inflammation and reductions in specialized pro-resolving mediators

Kymberly M. Gowdy1, Brita J. Kilburg-Basnyat1, Elizabeth Browder1, Sky Reece1, Myles Hodge1, Bin Luo1, Michael J. Yaeger1, Michael Odom1, Christine Psaltis1, Jonathan Manke2, Michael L. Armstrong2, Johanna L. Hannan1, N. Reisdorph2, Robert M. Tighe3, S. Raza Shaikh4

1East Carolina University, Greenville, NC, USA; 2University of Colorado, Denver, CO, USA; 3Duke University Medical Center, Durham, NC, USA; 4University of North Carolina Chapel Hill, NC, USA

Background. Ozone (O3), a criteria air pollutant, causes significant pulmonary morbidity and mortality. Recent epidemiological studies suggest that diet may influence the health effects associated with air pollution, including O3. Our previous studies indicate O3 exposure decreases pulmonary docosahexaenoic acid (DHA)-derived specialized pro-resolving mediators (SPMs). SPMs are lipid mediators produced at the site of injury that support resolution of the immune response and return of tissue homeostasis. Therefore, we hypothesize pulmonary inflammation noted after O3 exposure is due to a decrease in pulmonary SPM production that can be mitigated with dietary DHA supplementation.

Methods. Five-week-old C57Bl/6J (WT) male mice were fed a normal diet (ND) or a DHA supplemented diet (ND+2% DHA). After 6 weeks, mice were exposed to filtered air (FA) or 1 ppm O3 for 3h and necropsied 24h post-exposure. Bronchoalveolar lavage fluid (BAL) was assessed for cytokine production, cell counts/differentials, and protein. Pulmonary lipid mediators were quantified using LC-MS/MS.

Results. In O3-exposed groups, there were decreases in the pulmonary levels of DHA-derived SPM precursors 17-HDHA and 14-HDHA and the SPM Protectin DX. However, DHA supplementation prior to O3 mitigated these reductions in SPM precursors/SPMs. In the ND group, O3 exposure significantly increased BAL macrophages and neutrophils that was also reduced with dietary DHA supplementation. Compared to O3+ND, DHA reduced CCL2, CCL3, IL-6, and IL-1β cyto/chemokine expression in lung tissue.

Conclusions. Supplementing a diet with DHA increased pulmonary SPMs and their precursors resulted in a decrease in O3-induced cellular inflammation and expression of select cytokines and chemokines. These data support the novel idea that a DHA supplemented diet may mitigate O3-induced pulmonary responses.

 
POSTER
 

PUBLICATIONS

 

Kilburg-Basnyat B, Reece SW, Crouch MJ, Luo B, Boone AD, Yaeger M, Hodge M, Psaltis C, Hannan JL, Manke J, Armstrong ML, Reisdorph N, Tighe RM, Shaikh SR, Gowdy KM. Specialized Pro-Resolving Lipid Mediators Regulate Ozone-Induced Pulmonary and Systemic Inflammation. Toxicol Sci. 2018 Jun 1;163(2):466-477. doi: 10.1093/toxsci/kfy040.

Tighe RM, Birukova A, Yaeger MJ, Reece SW, Gowdy KM. Euthanasia- and Lavage-mediated Effects on Bronchoalveolar Measures of Lung Injury and Inflammation. Am J Respir Cell Mol Biol. 2018 Aug;59(2):257-266. doi: 10.1165/rcmb.2017-0357OC.