# Mechanisms of Adenosine Protection

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $349,875

## Abstract

ABSTRACT:
Mucosal inflammatory responses involve the early accumulation of neutrophils (PMN). Without
efficient PMN clearance at sites of infiltration, PMN can accumulate and contribute to chronic
inflammatory conditions, including ulcerative colitis (UC) and Crohn's disease (CD). Within
these diseases, there is significant interest in defining components of the inflammatory
microenvironment as a window to understanding molecular mechanisms of progression or
resolution.
Our ongoing studies for this renewal application have revealed that PMN transepithelial
migration (TEM) results in significant extracellular acidosis, in part through generation of large
amounts of lactate. Moreover, we demonstrate that PMN-derived adenosine (Ado)
significantly promotes pH homeostasis within the mucosal microenvironment. Based on thes
new studies, we hypothesize that PMN-derived Ado signaling elicits an adaptive tissue
response by promoting pH homeostasis to inflammatory acidity.
Three specific aims are directed at testing this hypothesis: In Specific Aim 1, we will elucidate
the lactate release and signaling axis in intestinal epithelia. In Specific Aim 2, we will extend
preliminary data to determine the mechanism(s) of Ado-mediated pH homeostasis during
PMN TEM. Specific Aim 3 will utilize murine models to probe the role of pH homeostasis in
protection afforded by Ado in vivo. The overall aim of this proposal is to identify novel
metabolic signaling mediated by Ado within the mucosa during inflammatory acidosis.

## Key facts

- **NIH application ID:** 10322159
- **Project number:** 5R01DK095491-09
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Sean P Colgan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $349,875
- **Award type:** 5
- **Project period:** 2012-06-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322159

## Citation

> US National Institutes of Health, RePORTER application 10322159, Mechanisms of Adenosine Protection (5R01DK095491-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10322159. Licensed CC0.

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