# Urothelial IL-6 Signaling in the Host Defense Against Urinary Tract Infections

> **NIH NIH K08** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2022 · $161,995

## Abstract

PROJECT SUMMARY/ABSTRACT
UTIs are a common source of patient morbidity that can result in permanent renal damage. Historically,
antibiotics have been the standard in UTI treatment and routinely used for prevention. However, the emergence
of multidrug resistant uropathogens limits the long-term viability of antimicrobial strategies based solely on
antibiotic therapy. As a result, alternative methods for UTI treatment and prevention are needed. The lining of
the urinary tract, or urothelium, serves essential roles in the detection and elimination of invading bacteria,
including production of cytokines and antimicrobial peptides (AMPs). These intrinsic qualities of innate defense
within the urothelium might be harnessed therapeutically to prevent and treat UTI. A fundamental knowledge
gap exists, however, in our understanding of how these different factors contribute to limiting UTI susceptibility.
The objective of this research project is to define the mechanisms by which the bladder urothelium defends the
urinary tract from invading uropathogenic bacteria. This proposal tests the hypothesis that the cytokine
interleukin-6 (IL-6) promotes clearance of uropathogenic Escherichia coli through activation of the Signal
transducer and activator of transcription 3 (Stat3) transcription factor and AMP production. The anticipated
outcome of this research is to establish the contributions of the IL-6/Stat3/AMP signal transduction cascade to
the host defense properties of the urothelium. Aim 1 will investigate how IL-6 directly limits urothelial
susceptibility to UTI. Aim 2 will establish the roles for urothelial Stat3 during UTI. Aim 3 will explore the impact
of AMPs in preventing UTI. Together, these Aims look to implicate the IL-6/Stat3/AMP pathway as a key driver
of urothelial susceptibility to UTI and thus as a potential target of UTI treatment. The completion of this award
will combine structured career development activities and mentored research programs to enable the transition
from a junior investigator to an independently funded surgeon-scientist.

## Key facts

- **NIH application ID:** 10397017
- **Project number:** 5K08DK122119-04
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Christina B Ching
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $161,995
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397017

## Citation

> US National Institutes of Health, RePORTER application 10397017, Urothelial IL-6 Signaling in the Host Defense Against Urinary Tract Infections (5K08DK122119-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10397017. Licensed CC0.

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