# SGK1 and the control of periodontal inflammation

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2021 · $368,719

## Abstract

Abstract
Host inflammatory immune responses to oral microbiota are tightly regulated by multiple pro-inflammatory and
anti-inflammatory mechanisms. The balance of there two activities ensures a state of immune homeostasis
which is critical for protecting against microbial invasion and avoiding subsequent collateral tissue damages.
To limit the ferocity of inflammation, a number of established pathways exist that dampen the innate immune
response. Our recent publication has demonstrated a novel role for serum- and glucocorticoid- inducible
kinase 1 (SGK1), a serine/threonine kinase associated with the PI3K pathway, in restraining the production of
E. coil LPS-mediated pro-inflammatory cytokine production in human monocytes. Preliminary data for this
application show for the first time that SGK1 is phospho-activated in human monocytes in response to
challenge with multiple oral bacteria. In addition, using P. gingivalis, a well-established model oral organism
for the investigation of host-pathogen interactions in the periodontium, we show that inhibition of SGK1 robustly
enhances the production of pro-inflammatory cytokines (TNF, IL-12, IL-6, IL-1β, IL-8) and reduces IL-10 levels,
a result also confirmed by using Cre-loxP-mediated SGK1 knockout mice. Moreover, the anti-inflammatory
role for SGK1 was validated by our preliminary in vivo evidence showing that systemic administration of the
SGK1 inhibitor, EMD638683, elevated infiltration of neutrophils and macrophages into the gingival tissues and
aggravated the severity of alveolar bone resorption in mice orally infected with P. gingivalis. Thus, we have
identified a novel role for SGK1 as a negative regulator of inflammation, and propose that stimulation of this
endogenous anti-inflammatory pathway in the host will help limit or prevent P. gingivalis-induced tissue
destruction. The specific hypothesis to be tested in this application is that in the context of P. gingivalis
challenge, SGK1 constrains the production of pro-inflammatory cytokines; down-regulates recruitment
of inflammatory cells to the periodontium; and in turn protects against alveolar bone loss through
downstream modification of inflammatory signaling molecules including Nedd4-2, MKP-1, and TAK1,
which ultimately converge on NF-κB. We will challenge this hypothesis with three specific Aims: (i) To
characterize SGK1 as an innate immune suppressor of inflammatory responses in vitro; (ii) To elucidate the
signaling mechanisms by which SGK1 controls host inflammatory responses; and (iii) To establish the in vivo
relevance of SGK1 in the control of host inflammation using mouse subcutaneous chamber and alveolar bone
loss models. Successful completion of these studies will characterize, for the first time, the anti-inflammatory
function of SGK1 in host inflammatory responses to P. gingivalis, and elucidate the novel anti-inflammatory
signaling network mediated by the SGK1-MKP1 module in the control of the inflammation progression. In the
...

## Key facts

- **NIH application ID:** 10179357
- **Project number:** 5R01DE026727-05
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Huizhi Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $368,719
- **Award type:** 5
- **Project period:** 2019-08-21 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179357

## Citation

> US National Institutes of Health, RePORTER application 10179357, SGK1 and the control of periodontal inflammation (5R01DE026727-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10179357. Licensed CC0.

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