# IL-27 receptor signaling in the maintenance of intestinal barrier after ethanol and burn injury

> **NIH NIH F30** · LOYOLA UNIVERSITY CHICAGO · 2020 · $32,332

## Abstract

Project Summary/Abstract
The goal of this project is to better understand how interleukin-27 (IL-27) signaling in intestinal epithelial cells
(IEC) can promote intestinal barrier integrity in the setting of ethanol intoxication and burn injury. Burn injuries
account for 40,000 hospitalizations every year, with nearly 50% of patients having detectable blood alcohol
levels at the time of admission. Patients intoxicated at the time of burn injury have worse clinical outcomes,
including longer hospital stays, increased rates of infection, and increased morbidity and mortality. Detrimental
sequelae of burn injuries are the result of the breakdown in the gut barrier, which normally encloses the largest
reservoir of bacteria and harmful bacterial products. Ethanol intoxication at the time of burn injury exacerbates
this post-burn pathogenesis, leading to exacerbated gut barrier dysfunction and leakiness. This gut barrier
breakdown leads to multiple organ failure, sepsis, and death following injury. A major contributing factor to gut
leakiness is attributed to hypoxic conditions in the gut, leading to stabilization of hypoxia inducible factor 1a
(HIF1a). Our lab has previously found that inhibition of HIF1a with PX-478 leads to improved outcomes in
ethanol intoxication and burn injury, including improved gut transit, decreased gut permeability, and reduced
inflammation. However, the mechanism by which this occurs is unknown. We have also found that expression
of the IL-27 receptor was restored in IECs following inhibition of HIF1a following ethanol intoxication and burn
injury. Ethanol intoxication and burn injury led to reduced IL-27 producing cells in the lamina propria, which is
accompanied by reduced IL-27 receptor expression in IECs. IL-27 has been implicated in restoring intestinal
barrier integrity in other models of intestinal inflammation, therefore leading us to hypothesize that restoring IL-
27 signaling following ethanol intoxication and burn injury will lead to improved barrier integrity. In Aim 1, we
will determine perturbations in IL-27 signaling in the intestine following HIF1a inhibition in ethanol intoxication
and burn injury. In Aim 2, we will elucidate the mechanism by which IL-27 signaling restores intestinal epithelial
barrier integrity by observing changes in phosphorylation of downstream signaling molecules STAT1/STAT3,
IEC proliferation, and tight junction expression. Overall, this study will aid in our understanding of how we can
restore intestinal barrier function following ethanol intoxication and burn injury.

## Key facts

- **NIH application ID:** 9907702
- **Project number:** 1F30DK123929-01
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Marisa Luck
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,332
- **Award type:** 1
- **Project period:** 2020-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9907702

## Citation

> US National Institutes of Health, RePORTER application 9907702, IL-27 receptor signaling in the maintenance of intestinal barrier after ethanol and burn injury (1F30DK123929-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9907702. Licensed CC0.

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