# A Targeted Approach to Managing Salivary Gland Inflammation Using Resolvins

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2022 · $367,971

## Abstract

ABSTRACT
Sjögren's syndrome (SS) is an autoimmune disease characterized by chronic inflammation and diminished
secretory function of the salivary glands (SG). Diagnostic features include dry mouth, lymphocytic infiltration
into the SG and presence of antinuclear autoantibodies in plasma. SS greatly decreases the patient’s quality of
life, and although extensive investigation has been done to understand it, causes of and effective treatments
for the disease are still unknown. In light of the high degree of need and the limitations of current therapies,
development of novel treatments to decrease inflammation and restore SG secretory function is essential. Our
previous studies demonstrated that SG express the AT-RvD1 receptor ALX/FPR2 to block pro-inflammatory
cytokine signaling, thereby promoting cell survival and tissue integrity in SS. More recently, we demonstrated
that AT-RvD1 treatment in SS-like NOD/ShiLtJ mice fully preserves secretory functioning, downregulates pro-
inflammatory cytokine expression and promotes pro-resolving signaling pathways. Encouraging as these
results may be, however, lymphocytic infiltration persists in AT-RvD1 treated SS mice, raising the possibility of
future pro-inflammatory cytokine production and possible recurrence of hypofunction. Moreover, we face
issues related to the properties of resolvins themselves that must be overcome for clinical applications to be
achieved. Specifically, a significant portion of administered resolvins (RvD1 included) do not reach their
intended destination with the desired regularity because they are quickly inactivated by eicosanoid
oxidoreductases (EOR) and their effects can be diffusely distributed throughout the body. Furthermore, the
problem of instability extends to the AT forms, which are somewhat less susceptible to inactivation. In addition
to these issues of durability, resolvins are relatively expensive, and when taken together, these concerns raise
questions about the feasibility of any treatment requiring large doses to be introduced into the blood stream. In
response, we believe that all of these issues may be addressed by infusing AT-RvD1 retrograde to the salivary
ducts, which could allow the benefits demonstrated by AT-RvD1 (i.e., preserved and/or restored saliva
secretion) to be retained while addressing areas of weakness discussed earlier. Moreover, to better exploit the
use of AT-RvD1, we will study the mechanisms by which it activates the ALX/FPR2 using a knock-out mouse
for this receptor (ALX/FPR2-/-). Next, we will describe the ALX/FPR2 signaling mechanisms in mouse and
human cells. Finally, we will determine whether ALX/FPR2 signaling pathways are altered in minor SG
biopsies (both with and without SS), thereby further extending our findings to the human disease. Our overall
hypothesis is that healthy SG functioning will be restored by local AT-RvD1 treatment. Aim 1 will demonstrate
the benefits of delivering AT-RvD1 locally for restoring SG function. Aim 2 wi...

## Key facts

- **NIH application ID:** 10386917
- **Project number:** 5R01DE027884-06
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Olga Juliana Baker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $367,971
- **Award type:** 5
- **Project period:** 2020-08-10 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10386917

## Citation

> US National Institutes of Health, RePORTER application 10386917, A Targeted Approach to Managing Salivary Gland Inflammation Using Resolvins (5R01DE027884-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10386917. Licensed CC0.

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