Abstract
Sjögren's syndrome (SS) is an autoimmune disorder characterized by chronic inflammation and destruction of salivary and lacrimal glands leading to dry mouth and dry eyes, respectively. Currently, the etiology of SS is unknown and the current therapies have no permanent benefit; therefore, new approaches are necessary to effectively treat this condition. Resolvins are highly potent endogenous lipid mediators that are synthesized during the resolution of inflammation to restore tissue homeostasis. Previous studies indicate that the resolvin family member, RvD1, binds to the ALX/FPR2 receptor to block inflammatory signals caused by tumor necrosis factor‐alpha (TNF‐α) in the salivary epithelium. More recently, the corticosteroid, dexamethasone (DEX), was shown to be effective in reducing salivary gland inflammation. However, DEX, as with other corticosteroids, elicits adverse secondary effects that could be ameliorated when used in smaller doses. Therefore, we investigated whether the more stable aspirin‐triggered (AT) epimer, AT‐RvD1, combined with reduced doses of DEX is effective in treating TNF‐α‐mediated disruption of polarized rat parotid gland (Par‐C10) epithelial cell clusters. Our results indicate that AT‐RvD1 and DEX individually reduced TNF‐α‐mediated alteration in the salivary epithelium (i.e., maintained cell cluster formation, increased lumen size, reduced apoptosis, and preserved cell survival signaling responses) as compared to untreated cells. Furthermore, AT‐RvD1 combined with a reduced dose of DEX produced stronger responses (i.e., robust salivary cell cluster formation, larger lumen sizes, further reduced apoptosis, and sustained survival signaling responses) as compared to those observed with individual treatments. These studies demonstrate that AT‐RvD1 combined with DEX is highly effective in treating TNF‐α‐mediated disruption of salivary gland epithelium.
Highlights
Sjo€gren’s syndrome (SS) is an autoimmune disease characterized by chronic inflammation and destruction of the salivary and lacrimal glands, leading to xerostomia and keratoconjunctivitis sicca (Miranda-Rius et al 2015)
Par-C10 cells were plated on GFR-MG and preincubated with tumor necrosis factor-a (TNF-a) followed by treatment with AT-Resolvin D1 (RvD1) and DEX alone and in combination as described in Materials and Methods
Par-C10 cells were plated on GFR-MG and preincubated with TNF-a followed by treatment with AT-RvD1 and 2016 | Vol 4 | Iss. 19 | e12990 Page 4
Summary
Sjo€gren’s syndrome (SS) is an autoimmune disease characterized by chronic inflammation and destruction of the salivary and lacrimal glands, leading to xerostomia and keratoconjunctivitis sicca (Miranda-Rius et al 2015). TNF-a is mainly produced by macrophages and lymphocytes, but is produced in salivary epithelial cells (Sisto et al 2009). Neutralization of TNF-a in non-obese diabetic (NOD) mice by transgenic expression of soluble TNF-receptor (p55) significantly reduced lymphocytic infiltration in submandibular and lacrimal glands associated with the decreased expression of the cell adhesion molecules, VCAM-1 and ICAM-1 (Hunger et al 1996). Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
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