title: ALX/FPR2 receptor for RvD1 is expressed and functional in salivary glands.
abstract: Sjögren's syndrome (SS) is an autoimmune disorder characterized by chronic inflammation and destruction of salivary and lacrimal glands, leading to dry mouth, dry eyes, and the presence of anti-nuclear antibodies. Despite modern advances, the current therapies for SS have no permanent benefit. A potential treatment could involve the use of resolvins, which are highly potent endogenous lipid mediators that are synthesized during the resolution of inflammation to restore tissue homeostasis. Our previous studies indicate that ALX/FPR2, the receptor for RvD1, is expressed and active in the rat parotid cell line Par-C10. Specifically, activation of ALX/FPR2 with RvD1 blocked inflammatory signals caused by TNF-α and enhanced salivary epithelial integrity. The goal of this study was to investigate RvD1 receptor expression and signaling pathways in primary salivary cells. Additionally, we determined the role of the aspirin-triggered 17R analog (AT-RvD1, a more chemically stable RvD1 epimeric form) in prevention of TNF-α-mediated salivary inflammation in mouse submandibular glands (mSMG). Our results indicate that ALX/FPR2 is expressed in mSMG and is able to elicit intracellular Ca2+ responses and phosphorylation of Erk1/2, as well as Akt. Given that these signaling pathways are linked to cell survival, we investigated whether AT-RvD1 was able to prevent programmed cell death in mSMG. Specifically, we determined that AT-RvD1 prevented TNF-α-mediated caspase-3 activation. Finally, we show that ALX/FPR2 is expressed in human minor salivary glands with and without SS, indicating the potential therapeutic use of AT-RvD1 for this condition.
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, New York; and.
authors.forename: Joel W
authors.initials: JW
authors.lastname: Nelson
authors.forename: Noel J
authors.initials: NJ
authors.lastname: Leigh
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Mellas
authors.forename: Andrew D
authors.initials: AD
authors.lastname: McCall
authors.forename: Alfredo
authors.initials: A
authors.lastname: Aguirre
authors.forename: Olga J
authors.initials: OJ
authors.lastname: Baker
mesh_terms: D000818:Animals; D004281:Docosahexaenoic Acids / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D044042:Receptors, Formyl Peptide / Q000096:biosynthesis*; D044067:Receptors, Lipoxin / Q000096:biosynthesis*; D012469:Salivary Glands / Q000473:pathology / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D012859:Sjogren's Syndrome / Q000378:metabolism / Q000473:pathology
chemical_list: C105101:FPR2 protein, human; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C518399:resolvin D1; D004281:Docosahexaenoic Acids
keywords: ALX/FPR2; AT-RvD1; GPR32; RvD1; Sjögren's syndrome; resolvins; salivary glands