# Dietary EPA mitigates ozone induced pulmonary inflammation through ChemR23 signaling

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $148,776

## Abstract

PROJECT SUMMARY
Premise and hypothesis: Ozone (O3) is a criteria air pollutant that increases the incidence of chronic pulmonary
diseases. The detrimental health effects upon O3 exposure occur in part through pulmonary inflammation
characterized by the production of cytokine/chemokines, suppression of alveolar macrophage phagocytosis,
and influx of inflammatory cells into the lung. At a molecular level, one of the ways O3 initiates pulmonary
inflammation is by altering lipid metabolism through increasing the biosynthesis of prostaglandins and
leukotrienes and decreasing the production of specialized pro-resolving mediators (SPMs). SPMs are critical
immunoresolvants with dual actions (i.e. they stop inflammation and trigger the resolution phase of
inflammation). Recently we have reported that O3 exposure leads a suppression in select SPMs and if
pulmonary levels are restored, pulmonary inflammation was reduced. Therefore, targeting SPM production is a
viable target to mitigate O3-induced pulmonary inflammation. In this application, we focus on the role of diet in
regulating pulmonary SPM production and the binding of these SPMs to receptors known to have downstream
signaling that blocks inflammatory responses upon O3 exposure. Specifically, dietary eicosapentaenoic acid
(EPA), an omega-3 polyunsaturated fatty acid that is poorly consumed in the western diet, may protect against
O3-induced pulmonary inflammation. EPA is the parent fatty acid that is metabolized to produce the SPM
family resolvin E (RvE) series. RvE1 is has been shown to be beneficial in resolving inflammation, restoring
tissue homeostasis, and deficiencies in RvE1 leads to the progression of multiple inflammatory diseases.
RvE1, in particular, binds the G-protein coupled receptor ERV1/ChemR23. Based on strong preliminary data,
we propose the central hypothesis that EPA blunts O3-induced pulmonary inflammation and promotes
resolution of injury through the downstream activation of the RvE1-ChemR23 axis. The hypothesis is
supported by preliminary data to show that O3 exposure reduces pulmonary expression of ChemR23,
ChemR23 deficient mice have more lung inflammation following exposure, and augmenting RvE1 levels
mitigates O3-induced pulmonary inflammation/injury. Approach: To define the role of dietary EPA in lung
inflammation and injury following O3, we propose two independent aims. In Aim 1, we will demonstrate that
dietary EPA improves O3-induced pulmonary inflammation and resolution of injury through the RvE1-ChemR23
axis utilizing EPA/RvE1 supplementation and a ChemR23-deficient mouse. In Aim 2, we will establish that
dietary EPA remodels the pulmonary lipidome during O3-induced pulmonary inflammation/resolution of
inflammation through the production of RvE1. The proposed aims will innovatively merge nutrition,
environmental health, lipid biochemistry, and immunology. Impact: Completion of this proposal will: 1)
provide the scientific rationale for clinical EPA supplementation st...

## Key facts

- **NIH application ID:** 10506938
- **Project number:** 3R01ES031378-03S1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Kymberly Mae Gowdy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $148,776
- **Award type:** 3
- **Project period:** 2020-05-20 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10506938

## Citation

> US National Institutes of Health, RePORTER application 10506938, Dietary EPA mitigates ozone induced pulmonary inflammation through ChemR23 signaling (3R01ES031378-03S1). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10506938. Licensed CC0.

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