# Redox Regulation of Gingival Inflammation

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2020 · $442,466

## Abstract

Project Summary Abstract
PI: Bagaitkar
Periodontal diseases are highly common infectious diseases. Chronic inflammation in periodontitis results in the
progressive destruction of hard and soft tissues and enhances susceptibility to other systemic disease. The host
factors that regulate the magnitude, nature and persistence of inflammatory responses in the oral are
incompletely understood. We have previously shown that reactive oxygen species (ROS) generated by the
activation of leukocyte NADPH oxidase enzyme complex plays a critical role in dampening hyperinflammatory
responses. Oxidase deficiency in mice resulted in profound inflammation characterized by dysregulated
neutrophil and macrophages responses and resolution delays. These data support a somewhat counterintuitive
role for ROS in limiting host inflammation. Whether oxidants modulate inflammatory pathways in the oral cavity
is unclear. Our central hypothesis is that the NADPH oxidase derived-ROS, independent of their antimicrobial
functions, play key roles in redox modulation of neutrophil and macrophage effector functions in vitro and in vivo.
Further, we hypothesize that while excessive amounts of ROS are associated with the pathophysiology of
periodontal diseases, low-level, localized ROS responses are immuno-regulatory. These hypotheses will be
tested in two specific aims. 1) Determine the role of NADPH oxidase in the regulation of PMN effector functions
in acute responses in the gingiva. 2) Determine the role of NADPH oxidase in the modulation of macrophage
function and resolution of gingival inflammation. The use of conditional knockout mice that lack NADPH oxidase
activity selectively in neutrophils or macrophages will enable us to specifically determine the role of oxidants in
a cell intrinsic manner in vivo. The data generated by these studies will shed key mechanistic insights in our
understanding of immune pathways relevant in gingival inflammation and their regulation by oxidants. Further,
our studies are also highly relevant in understanding the immunopathology of chronic granulomatous disease, a
life-threatening immunodeficiency caused by inherited mutations in NADPH oxidase subunit genes.

## Key facts

- **NIH application ID:** 9885641
- **Project number:** 1R01DE028296-01A1
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Juhi Bagaitkar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $442,466
- **Award type:** 1
- **Project period:** 2019-12-09 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9885641

## Citation

> US National Institutes of Health, RePORTER application 9885641, Redox Regulation of Gingival Inflammation (1R01DE028296-01A1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9885641. Licensed CC0.

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