Dietary Eicosapentaenoic Acid Improves Ozone-Induced Pulmonary Inflammation in C57/BL6 Mice.

Abstract

Ambient concentrations of the air pollutant, ozone, are rising with increasing global temperatures. Ozone is known to increase incidence and exacerbation of chronic lung diseases, which will increase as ambient ozone levels rise. Studies have identified diet as a variable able to modulate the pulmonary health effects associated with ozone exposure. Eicosapentaenoic Acid (EPA) is an n-3 polyunsaturated fatty acid (PUFA) consumed through diet that lowers inflammation through conversion to oxylipins including Hydroxy Eicosapentaenoic Acids (HEPEs). However, the role of dietary EPA in ozone-induced pulmonary inflammation is unknown. Therefore, we hypothesize increasing dietary EPA will decrease ozone-induced pulmonary inflammation and injury through the production of HEPEs. To test this, male C57BL/6J mice were fed a purified control diet or EPA-supplemented diet for 4 weeks and then exposed to filtered air (FA) or 1 part per million ozone for 3 hours. 24 or 48 hours post exposure, bronchoalveolar lavage (BAL) fluid was collected to assess airspace inflammation/injury and lung tissue was collected for targeted Liquid Chromatography-Mass Spectrometry (LC-MS/MS) lipidomics. Following ozone exposure, EPA supplementation did not alter markers of lung injury, but decreased ozone-induced airspace neutrophilia. LC-MS/MS targeted lipidomics reveal dietary EPA supplementation increased pulmonary EPA-derived metabolites including 5-HEPE and 12-HEPE. Additionally, EPA supplementation decreased pulmonary levels of pro-inflammatory Arachidonic Acid (AA)-derived metabolites. To evaluate if dietary EPA reduces ozone-induced pulmonary inflammation through increased pulmonary HEPEs, C57BL/6J mice were administered 5- and 12-HEPEs systemically prior to filtered air or ozone exposure. Pretreatment with 5- and 12-HEPEs reduced ozone-driven increases in airspace macrophages. Together, these data indicate that an EPA-supplemented diet protects against ozone-induced airspace inflammation which is, in part, due to increasing pulmonary concentrations of 5- and 12-HEPEs. These findings suggest that dietary EPA and/or increasing EPA-derived metabolites in the lung can reduce ozone-driven incidences and exacerbations of chronic pulmonary diseases.