# Interrogating the Effects of Aging on Influenza Infections: The Role of Prostaglandin E2

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $38,245

## Abstract

Project Summary
Influenza disproportionally affects older people, with ~80% of all influenza-related deaths occurring in the >65
years of age population. This is of increasing concern as the average age of the World population continues to
grow. Therefore, there is a critical need to understand the age-related dysfunctions of the immune system in
order to develop novel anti-influenza virus (IAV) therapies targeted for older people.
Previous work by our lab has shown that alveolar macrophages (AM) are essential for the host response
against IAV. Additionally, we have shown that aging limits AM numbers and ability to resolve neutrophilic
inflammation within the lungs following an IAV infection. However, factors within the aged-lung environment
that contributes to these impairments of AM have yet to be identified. Our preliminary data shows that aging
leads to elevated levels of prostaglandin E2 (PGE2), an immunosuppressive lipid, in the bronchial alveolar
lavage fluid (BALF) both prior to and during an IAV infection. We hypothesize that the age-associated
elevations of PGE2 impair the functions of alveolar macrophages within the airways. We will test this
hypothesis by an ex vivo culture of AMs with PGE2 and by blocking PGE2 signaling in vivo with receptor
antagonists. Additionally, to obtain a comprehensive understanding of PGE2 regulation on AMs, RNA-seq
analysis will be performed on AMs isolated from young and aged mice and cultured with or without PGE2.
We also plan on identifying the main cellular sources and mechanisms behind the age-associated elevation of
PGE2. Our preliminary data suggests that type II alveolar epithelial cells (AECIIs) are the primary producers of
PGE2 and that their secretion of PGE2 increases with host age. However, the mechanisms contributing to the
increased PGE2 secretion by AECIIs are unidentified. We hypothesize that age-enhanced signaling of p38, a
mitogen-activated protein kinase (MAPK), within AECIIs promotes PGE2 production. We will test this
hypothesis using p38 inhibitors in both primary ex vivo cultures and in vivo murine models. Additionally, we will
utilize a transgenic murine model in which p38α, the primary isoform of p38 associated with inflammation, is
specifically deleted form AECIIs.
The results from these studies will further our understanding of how aging impacts innate immunity and can
potentially provide novel targets for the development of anti-IAV therapies. Importantly, results of this study can
potentially be extrapolated to other respiratory viral infections. This project will also serve as excellent training
for the applicant, Judy Chen, to gain skills that are central for research and critical thinking to help her become
a successful, independent scientist.

## Key facts

- **NIH application ID:** 10228859
- **Project number:** 1F31HL158003-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Judy Chen
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,245
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228859

## Citation

> US National Institutes of Health, RePORTER application 10228859, Interrogating the Effects of Aging on Influenza Infections: The Role of Prostaglandin E2 (1F31HL158003-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10228859. Licensed CC0.

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