Expression of Resolvin D1 Biosynthetic Pathways in Salivary Epithelium

Leigh, Noel J.; Nelson, James W.; Mellas, Rachel E.; Aguirre, Alfredo; Baker, Olga J.

doi:10.1177/0022034513519108

Cited by 24 publications

(22 citation statements)

References 29 publications

(37 reference statements)

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“…ALX/FPR2 is also expressed in mouse submandibular gland (SMG), and its activation with AT-RvD1 increases a diverse set of intracellular signaling pathways (e.g., intracellular calcium [Ca 2+ ] i , Erk1/2, and Akt) to block TNF-α-mediated caspase-3 activation [14]. We also demonstrated that the machinery for RvD1 biosynthesis and its receptor are expressed and functional in human minor salivary glands (hMSG) with and without SS [15]. The expression levels of ALX/FPR2 seem to be unaltered in hMSG with and without SS [15], indicating that RvD1 could be used as a therapeutic option to treat salivary gland inflammation in SS patients.…”

Section: Introductionmentioning

confidence: 99%

“…We also demonstrated that the machinery for RvD1 biosynthesis and its receptor are expressed and functional in human minor salivary glands (hMSG) with and without SS [15]. The expression levels of ALX/FPR2 seem to be unaltered in hMSG with and without SS [15], indicating that RvD1 could be used as a therapeutic option to treat salivary gland inflammation in SS patients.…”

Section: Introductionmentioning

confidence: 99%

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Aspirin-Triggered Resolvin D1 Versus Dexamethasone in the Treatment of Sjögren's Syndrome-Like NOD/ShiLtJ Mice - A Pilot Study

et al. 2015

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aspirin-Triggered Resolvin D1 Versus Dexamethasone in the Treatment of Sjögren's Syndrome-Like NOD/ShiLtJ Mice - A Pilot Study

et al. 2015

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“…Both RvD1 receptors are PTX‐sensitive and do not employ the classical Ca 2+ or cAMP second messengers in PMN cells (Krishnamoorthy et al , ). More recently, however, RvD1 was found to elicit a Ca 2+ response and increase Akt phosphorylation in salivary epithelial cells, suggesting that ALX/FPR2 could activate PI3K pathways in some salivary cells (Leigh et al , ; Nelson et al , ). RvD2 binds to GPR18, also known as DRV2, to activate cAMP signaling (Chiang et al , ).…”

Section: Lipid Mediators Involved In Inflammationmentioning

confidence: 99%

“…RvD1 has recently been of interest for the mitigation of salivary gland inflammation. For example, RvD1 biosynthetic pathways have been discovered in the salivary gland epithelium (Leigh et al , ), and RvD1 blocks cytokine signaling in salivary epithelium to promote cell survival and tissue integrity in rat parotid Par‐C10 cells (Odusanwo et al , ). This was also shown to be true in mouse submandibular gland (SMG) cells coupled with the confirmation of the presence and functionality of the ALX/FPR2 (Nelson et al , ).…”

Section: Lipid Mediators Involved In Inflammationmentioning

confidence: 99%

Regulation of inflammation by lipid mediators in oral diseases

Sommakia

Baker

2016

Oral Diseases

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Lipid mediators (LM) of inflammation are a class of compounds derived from ω-3 and ω-6 fatty acids that play a wide role in modulating inflammatory responses. Some LM possess pro-inflammatory properties, while others possess pro-resolving characteristics, and the class switch from pro-inflammatory to pro-resolving is crucial for tissue homeostasis. In this article, we review the major classes of LM, focusing on their biosynthesis and signaling pathways, and their role in systemic and, especially, oral health and disease. We discuss the detection of these LM in various body fluids, focusing on diagnostic and therapeutic applications. We also present data showing gender-related differences in salivary LM levels in healthy controls, leading to a hypothesis on the etiology of inflammatory diseases, particularly, Sjögren’s Syndrome. We conclude by enumerating open areas of research where further investigation of LM is likely to result in therapeutic and diagnostic advances.

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“…Moreover, RvD1 biosynthetic pathways are expressed and functional in the human and mouse salivary epithelium (Leigh et al. ).…”

Section: Introductionmentioning

confidence: 99%

AT-RvD1 combined with DEX is highly effective in treating TNF-α-mediated disruption of the salivary gland epithelium

et al. 2016

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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.

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Expression of Resolvin D1 Biosynthetic Pathways in Salivary Epithelium

Cited by 24 publications

References 29 publications

Aspirin-Triggered Resolvin D1 Versus Dexamethasone in the Treatment of Sjögren's Syndrome-Like NOD/ShiLtJ Mice - A Pilot Study

Aspirin-Triggered Resolvin D1 Versus Dexamethasone in the Treatment of Sjögren's Syndrome-Like NOD/ShiLtJ Mice - A Pilot Study

Regulation of inflammation by lipid mediators in oral diseases

AT-RvD1 combined with DEX is highly effective in treating TNF-α-mediated disruption of the salivary gland epithelium

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