A combination treatment of low-dose dexamethasone and aspirin-triggered resolvin D1 reduces Sjögren syndrome–like features in a mouse modelWhy Is This Important?
Background: Sjögren syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration and diminished secretory function of the salivary glands. Dexamethasone (DEX) resolves dry mouth and lymphocytic infiltration; however, this treatment is difficult to maintain because of multiple adv...
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Elsevier
2023-01-01
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| Series: | JADA Foundational Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772414X22000123 |
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| author | Harim Tavares dos Santos, DDS, PhD Frank Maslow, BS Kihoon Nam, PhD Bryan Trump, DDS Gary A. Weisman, PhD Olga J. Baker, DDS, PhD |
| author_facet | Harim Tavares dos Santos, DDS, PhD Frank Maslow, BS Kihoon Nam, PhD Bryan Trump, DDS Gary A. Weisman, PhD Olga J. Baker, DDS, PhD |
| author_sort | Harim Tavares dos Santos, DDS, PhD |
| collection | DOAJ |
| description | Background: Sjögren syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration and diminished secretory function of the salivary glands. Dexamethasone (DEX) resolves dry mouth and lymphocytic infiltration; however, this treatment is difficult to maintain because of multiple adverse effects (eg, osteoporosis and skin thinning); likewise, aspirin-triggered resolvin D1 (AT-RvD1) increases saliva secretion but cannot eliminate lymphocytic infiltration. Previous studies showed that a combination of low-dose DEX with AT-RvD1 before disease onset prevents SS-like features in a mouse model; however, this is not clinically practical because there are no reliable indicators of SS before disease onset. Therefore, the authors applied the combined treatment at disease onset to show its efficacy and comparative lack of adverse effects, so that it may reasonably be maintained over a patient’s lifetime. Methods: NOD/ShiLtJ mice were treated with ethanol (vehicle control), high-dose DEX alone, AT-RvD1 alone, or a combination of low-dose DEX with AT-RvD1 at disease onset for 8 weeks. Then saliva flow rates were measured, and submandibular glands were harvested for histologic analyses. Results: A combined treatment of low-dose DEX with AT-RvD1 significantly decreased mast cell degranulation and lymphocytic infiltration, increased saliva secretion, and restored apical aquaporin-5 expression in submandibular glands of NOD/ShiLtJ mice. Conclusions: Low-dose DEX combined with AT-RvD1 reduces the severity of SS-like manifestation and prevents the development of advanced and potentially irreversible damage, all in a form that can reasonably be administered indefinitely without the need to cease treatment because of secondary effects. |
| format | Article |
| id | doaj-art-5e5c39691cd840bb835263cf392bda86 |
| institution | OA Journals |
| issn | 2772-414X |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JADA Foundational Science |
| spelling | doaj-art-5e5c39691cd840bb835263cf392bda862025-08-20T02:27:39ZengElsevierJADA Foundational Science2772-414X2023-01-01210001610.1016/j.jfscie.2022.100016A combination treatment of low-dose dexamethasone and aspirin-triggered resolvin D1 reduces Sjögren syndrome–like features in a mouse modelWhy Is This Important?Harim Tavares dos Santos, DDS, PhD0Frank Maslow, BS1Kihoon Nam, PhD2Bryan Trump, DDS3Gary A. Weisman, PhD4Olga J. Baker, DDS, PhD5Department of Otolaryngology, Head and Neck Surgery, University of Missouri, Columbia, MO; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MODepartment of Otolaryngology, Head and Neck Surgery, University of Missouri, Columbia, MO; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MODepartment of Otolaryngology, Head and Neck Surgery, University of Missouri, Columbia, MO; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MOSchool of Dentistry and Department of Dermatology, University of Utah, Salt Lake City, UTChristopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO; Department of Biochemistry, University of Missouri, Columbia, MODepartment of Otolaryngology, Head and Neck Surgery, University of Missouri, Columbia, MO; Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO; Department of Biochemistry, University of Missouri, Columbia, MO; Address correspondence to Dr Baker.Background: Sjögren syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration and diminished secretory function of the salivary glands. Dexamethasone (DEX) resolves dry mouth and lymphocytic infiltration; however, this treatment is difficult to maintain because of multiple adverse effects (eg, osteoporosis and skin thinning); likewise, aspirin-triggered resolvin D1 (AT-RvD1) increases saliva secretion but cannot eliminate lymphocytic infiltration. Previous studies showed that a combination of low-dose DEX with AT-RvD1 before disease onset prevents SS-like features in a mouse model; however, this is not clinically practical because there are no reliable indicators of SS before disease onset. Therefore, the authors applied the combined treatment at disease onset to show its efficacy and comparative lack of adverse effects, so that it may reasonably be maintained over a patient’s lifetime. Methods: NOD/ShiLtJ mice were treated with ethanol (vehicle control), high-dose DEX alone, AT-RvD1 alone, or a combination of low-dose DEX with AT-RvD1 at disease onset for 8 weeks. Then saliva flow rates were measured, and submandibular glands were harvested for histologic analyses. Results: A combined treatment of low-dose DEX with AT-RvD1 significantly decreased mast cell degranulation and lymphocytic infiltration, increased saliva secretion, and restored apical aquaporin-5 expression in submandibular glands of NOD/ShiLtJ mice. Conclusions: Low-dose DEX combined with AT-RvD1 reduces the severity of SS-like manifestation and prevents the development of advanced and potentially irreversible damage, all in a form that can reasonably be administered indefinitely without the need to cease treatment because of secondary effects.http://www.sciencedirect.com/science/article/pii/S2772414X22000123Salivary glandsinflammationresolvinssteroidslipid mediators |
| spellingShingle | Harim Tavares dos Santos, DDS, PhD Frank Maslow, BS Kihoon Nam, PhD Bryan Trump, DDS Gary A. Weisman, PhD Olga J. Baker, DDS, PhD A combination treatment of low-dose dexamethasone and aspirin-triggered resolvin D1 reduces Sjögren syndrome–like features in a mouse modelWhy Is This Important? JADA Foundational Science Salivary glands inflammation resolvins steroids lipid mediators |
| title | A combination treatment of low-dose dexamethasone and aspirin-triggered resolvin D1 reduces Sjögren syndrome–like features in a mouse modelWhy Is This Important? |
| title_full | A combination treatment of low-dose dexamethasone and aspirin-triggered resolvin D1 reduces Sjögren syndrome–like features in a mouse modelWhy Is This Important? |
| title_fullStr | A combination treatment of low-dose dexamethasone and aspirin-triggered resolvin D1 reduces Sjögren syndrome–like features in a mouse modelWhy Is This Important? |
| title_full_unstemmed | A combination treatment of low-dose dexamethasone and aspirin-triggered resolvin D1 reduces Sjögren syndrome–like features in a mouse modelWhy Is This Important? |
| title_short | A combination treatment of low-dose dexamethasone and aspirin-triggered resolvin D1 reduces Sjögren syndrome–like features in a mouse modelWhy Is This Important? |
| title_sort | combination treatment of low dose dexamethasone and aspirin triggered resolvin d1 reduces sjogren syndrome like features in a mouse modelwhy is this important |
| topic | Salivary glands inflammation resolvins steroids lipid mediators |
| url | http://www.sciencedirect.com/science/article/pii/S2772414X22000123 |
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