Nelson JW, Leigh NJ, Mellas RE, McCall AD, Aguirre A, Baker OJ. ALX/FPR2 receptor for RvD1 is expressed and functional in salivary glands.

No abstract

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.

Saliva plays a major role in maintaining oral health. Patients with salivary hypofunction exhibit difficulty in chewing and swallowing foods, tooth decay, periodontal disease, and microbial infections. At this time, treatments for hyposalivation are limited to medications (e.g., muscarinic receptor agonists: pilocarpine and cevimeline) that induce saliva secretion from residual acinar cells as well as artificial salivary substitutes. Therefore, advancement of restorative treatments is necessary to improve the quality of life in these patients. Our previous studies indicated that salivary cells are able to form polarized 3-dimensional structures when grown on growth factor-reduced Matrigel. This basement membrane is rich in laminin-III (L1), which plays a critical role in salivary gland formation. Mitotically inactive feeder layers have been used previously to support the growth of many different cell types, as they provide factors necessary for cell growth and organization. The goal of this study was to improve salivary gland cell differentiation in primary cultures by using a combination of L1 and a feeder layer of human hair follicle-derived mesenchymal stem cells (hHF-MSCs). Our results indicated that the direct contact of mouse submandibular (mSMG) cell clusters and hHF-MSCs was not required for mSMG cells to form acinar and ductal structures. However, the hHF-MSC conditioned medium enhanced cell organization and multilumen formation, indicating that soluble signals secreted by hHFMSCs play a role in promoting these features.