# Redox-mediated regulation of pattern-recognition-receptor signaling in intestinal epithelial cells

> **NIH NIH R03** · BOSTON CHILDREN'S HOSPITAL · 2020 · $132,750

## Abstract

PROJECT SUMMARY
The intestinal epithelium is a critical mucosal barrier that mediates communication between the intestinal
luminal environment and the immune system. Several lines of evidence suggest that stable reactive oxygen
species (ROS) play an important role in regulating cell signaling at mucosal surfaces, both in response to the
microbial environment and in gut inflammation. Stable ROS such as hydrogen peroxide (H2O2) can be
generated by epithelial cells through the NADPH oxidase enzyme family (e.g. NOX1) or from other
environmental sources such as bacteria. H2O2 modulates cellular signaling via oxidative modifications of
target cysteine residues on proteins, altering downstream functions. However, exactly what signaling proteins
and pathways are impacted by ROS during inflammation is poorly understood and may provide key
information in understanding the pathogenesis of inflammatory bowel diseases and the development of
biomarkers to track disease activity.
Our recent data shows that NOX1-generated H2O2 can be transported through aquaporin channels (AQP3)
and is important in mediating epithelial environmental responses. Our studies have also shown that
epithelial signaling, in response to pattern-recognition-receptor ‘danger’ signals such as interleukin-1 beta
(IL-1b), is also H2O2-dependent. To further investigate proteins that are selectively oxidized in the presence
of IL-1b we carried out redox proteomics of mouse primary intestinal epithelial cells. We discovered several
candidate proteins that are selectively oxidized in a NOX1 and AQP3-dependent manner, including
Peroxiredoxin 6 (PRDX6) - a known multifunctional redox-sensitive protein. Aim 1 of this R03 proposal will
therefore test the hypothesis that PRDX6 function is important for epithelial pattern-recognition-receptor
signaling. Aim 2 takes a proteomics approach to identify key redox-modified proteins in human disease by
investigating pattern-recognition-receptor responses using colonoids derived from healthy individuals and
individuals with inflammatory bowel disease. The main goals of these studies are to identify novel redox-
dependent signaling pathways in intestinal epithelial cells during inflammatory danger signaling and to use
this data to develop novel therapeutic approaches for mucosal inflammatory diseases.

## Key facts

- **NIH application ID:** 10041287
- **Project number:** 1R03DK125630-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Jay Thiagarajah
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $132,750
- **Award type:** 1
- **Project period:** 2020-08-11 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10041287

## Citation

> US National Institutes of Health, RePORTER application 10041287, Redox-mediated regulation of pattern-recognition-receptor signaling in intestinal epithelial cells (1R03DK125630-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10041287. Licensed CC0.

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