Aspirin-Triggered Resolvin D1 Versus Dexamethasone in the Treatment of Sjögren's Syndrome-Like NOD/ShiLtJ Mice - A Pilot Study.
Resolvin D1 (RvD1) and its aspirin-triggered epimeric form (AT-RvD1) are endogenous lipid mediators (derived from docosahexaenoic acid, DHA) that control the duration and magnitude of inflammation in models of complex diseases. Our previous studies demonstrated that RvD1-mediated signaling pathways are expressed and active in salivary glands from rodents and humans. Furthermore, treatment of salivary cells with RvD1 blocked TNF-α-mediated inflammatory signals and improved epithelial integrity. The purpose of this pilot study was to determine the feasibility of treatment with AT-RvD1 versus dexamethasone (DEX) on inflammation (i.e., lymphocytic infiltration, cytokine expression and apoptosis) observed in submandibular glands (SMG) from the NOD/ShiLtJ Sjögren's syndrome (SS) mouse model before experimenting with a larger population. NOD/ShiLtJ mice were treated intravenously with NaCl (0.9%, negative control), AT-RvD1 (0.01-0.1 mg/kg) or DEX (4.125-8.25 mg/kg) twice a week for 14 weeks beginning at 4 weeks of age. At 18 weeks of age, SMG were collected for pathological analysis and detection of SS-associated inflammatory genes. The AT-RvD1 treatment alone did not affect lymphocytic infiltration seen in NOD/ShiLtJ mice while DEX partially prevented lymphocytic infiltration. Interestingly, both AT-RvD1 and DEX caused downregulation of SS-associated inflammatory genes and reduction of apoptosis. Results from this pilot study suggest that a systemic treatment with AT-RvD1 and DEX alone attenuated inflammatory responses observed in the NOD/ShiLtJ mice; therefore, they may be considered as potential therapeutic tools in treating SS patients when used alone or in combination.
School of Dentistry, University of Utah, Salt Lake City, UT 84108-1201, USA.
Justin T
JT
Easley
School of Dentistry, University of Utah, Salt Lake City, UT 84108-1201, USA.
Joel W
JW
Nelson
School of Dentistry, University of Utah, Salt Lake City, UT 84108-1201, USA.
Rachel E
RE
Mellas
School of Dentistry, University of Utah, Salt Lake City, UT 84108-1201, USA.
Salah
S
Sommakia
School of Dentistry, University of Utah, Salt Lake City, UT 84108-1201, USA.
Chunhua
C
Wu
School of Dentistry, University of Utah, Salt Lake City, UT 84108-1201, USA.
Bryan
B
Trump
School of Dentistry, University of Utah, Salt Lake City, UT 84108-1201, USA.
Olga J
OJ
Baker
AT-RvD1; Cytokine; Resolvins; RvD1; Salivary Glands; Sjögren’s syndrome; Submandibular Gland