AT-RvD1 combined with DEX is highly effective in treating TNF-α-mediated disruption of the salivary gland epithelium.
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.
School of Dentistry, University of Utah, Salt Lake City, Utah.
Justin T
JT
Easley
School of Dentistry, University of Utah, Salt Lake City, Utah.
Christina L M
CL
Maruyama
School of Dentistry, University of Utah, Salt Lake City, Utah.
Ching-Shuen
CS
Wang
School of Dentistry, University of Utah, Salt Lake City, Utah olga.baker@hsc.utah.edu.
Olga J
OJ
Baker
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D003131:Combined Modality Therapy / Q000379:methods*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D051381:Rats; D044067:Receptors, Lipoxin / Q000187:drug effects / Q000378:metabolism; D012469:Salivary Glands / Q000166:cytology* / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology; D012859:Sjogren's Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005938:Glucocorticoids; D044067:Receptors, Lipoxin; D014409:Tumor Necrosis Factor-alpha; C482540:lipoxin A(4) receptor, rat; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D003907:Dexamethasone; D001241:Aspirin
ALX/FPR2; AT‐RvD1; RvD1; Sjögren's syndrome; salivary glands
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