# RvD1-FPR2 signaling ameliorates alcoholic liver disease

> **NIH NIH F32** · UNIVERSITY OF LOUISVILLE · 2022 · $32,580

## Abstract

Alcoholic hepatitis (AH) is a morbid condition with poor prognosis that is primarily driven by altered
immune cell function in response to endotoxemia, but the mechanisms are not fully known or
understood. Resolvin D1 (RvD1) is a pro-resolution lipid mediator that signals through formyl
peptide receptor 2 (FPR2) in mice eliciting M2 polarization in macrophages and antibacterial
functions in neutrophils. Plasma RvD1 levels and hepatic FPR2 expression are decreased in AH
patients suggesting this pathway is impeded in AH. Animal models suggest RvD1 treatment
ameliorates alcohol induced liver injury, inflammation, fibrosis, and endotoxemia while Fpr2-/- mice
develop exacerbated liver injury, inflammation, fibrosis, and endotoxemia. Studies characterizing
the RvD1-FPR2 signaling pathway in alcoholic liver disease (ALD) are nonexistent but are
warranted based on preliminary data. Aim 1: This aim will determine if RvD1 acts solely through
FPR2 to elicit protection in an animal of alcoholic liver disease (ALD). Aim 2: Aim 2a will determine
if the RvD1-FPR2 signaling pathway is essential for M2 polarization of Kupffer cells. Aim 2b will
establish if RvD1-FPR2 signaling is required for neutrophil-mediated defense responses against
pathogenic threats. Aim 3: AH patient and healthy control acquired neutrophils and monocytes
will be treated with or without RvD1 ex vivo followed by flow cytometry and proteomic and
phosphoproteomic analysis to measure receptor activation and to characterize the signaling
pathway, respectively. Collectively this study will generate data that could identify RvD1 or FPR2
agonists as a therapeutic approach for ALD. Due to the severity of AH and the analysis of AH
patient samples this study it is immediately impactful and informative for future treatment
strategies. Novel biomarkers and therapeutic interventions are expected to come from the
conclusion of the proposed study. Basic biology of the RvD1-FPR2 signaling pathway in
neutrophils and monocytes is expected from this work as well.

## Key facts

- **NIH application ID:** 10380761
- **Project number:** 5F32AA027950-03
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Josiah E Hardesty
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $32,580
- **Award type:** 5
- **Project period:** 2020-05-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380761

## Citation

> US National Institutes of Health, RePORTER application 10380761, RvD1-FPR2 signaling ameliorates alcoholic liver disease (5F32AA027950-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10380761. Licensed CC0.

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