Saliva Secretion Improves in AT-RvD1- and Dexamethasone-treated NOD/ShiLtj Mice

Objectives: Sjögren’s syndrome (SS) is an autoimmune disease that causes hyposalivation resulting in patient discomfort, alterations in the oral microflora, and susceptibility to caries. Currently there is no effective treatment for SS, thus alternative approaches are needed. Resolvins are endogenous lipid mediators that promote the resolution of inflammation. Our previous studies showed that treatment of NOD/ShiLtj mouse before disease onset with resolvins (AT-RvD1) and dexamethasone (DEX) is successful in preventing SS phenotypes. Therefore, the objective of this study is to determine if treating mice with AT-RvD1 and DEX after disease onset will reverse disease phenotypes (i.e., saliva secretion as well as aquaporin-5 (AQP5) and zonula occludens (ZO-1) tight junction expression and localization in submandibular glands, SMG).
Methods: Female and male NOD/ShiLtJ at 12-wk and 16-wk respectively were treated twice a week via tail vein injection for 4-wk with AT-RvD1 (0.1 mg/kg) and (DEX 4.125 mg/kg) alone and in combination as well as with ethanol (7.2%) as vehicle control. Female and male mice at 20-wk and 24-wk of age respectively were anesthetized with 100 mg/kg ketamine and 5 mg/kg xylaxine and euthanized. SMG were dissected, fixed and paraffin sectioned and confocal analysis conducted. Additionally, saliva secretion in response to pilocarpine-HCl/PBS (10 mg/kg) was measured.
Results: Treatment with AT-RvD1 and DEX alone and in combination restored saliva flow rates as compared to vehicle controls. Moreover, we observed that AT-RvD1 and DEX alone and in combination restored apical ZO-1 expression and localization as compared to vehicle controls in SMG. Finally, AQP5 apical staining did not show significant changes between the groups.
Conclusions: Our results indicate that treatment with AT-RvD1 and DEX alone and in combination reverses SS phenotypes including improved saliva secretion and tight junction integrity.