1. Aspirin Triggered Resolvin D1 reduces inflammation and restores saliva secretion in a Sjögren's syndrome mouse model
- Author
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Bryan G. Trump, Ching Shuen Wang, Olga J. Baker, Kihoon Nam, Spencer M. Dean, and Christina L. Maruyama
- Subjects
Male ,medicine.medical_specialty ,Docosahexaenoic Acids ,Lymphocyte ,medicine.medical_treatment ,Saliva secretion ,Drug Evaluation, Preclinical ,Inflammation ,Formyl peptide receptor 2 ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Mice, Inbred NOD ,Internal medicine ,medicine ,Animals ,Pharmacology (medical) ,030212 general & internal medicine ,Lymphocyte Count ,Saliva ,030203 arthritis & rheumatology ,Aspirin ,Basic and Translational Science ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Submandibular gland ,Disease Models, Animal ,Endocrinology ,medicine.anatomical_structure ,Cytokine ,Sjogren's Syndrome ,Cytokines ,Th17 Cells ,Female ,Interleukin 17 ,medicine.symptom ,Inflammation Mediators ,business ,Salivation ,medicine.drug - Abstract
Objectives SS is characterized by chronic inflammation of the salivary glands leading to loss of secretory function, thereby suggesting specialized pro-resolving mediators targeting inflammation to be a viable option for treating SS. Previous studies demonstrated that aspirin-triggered resolvin D1 (AT-RvD1) prevents chronic inflammation and enhances saliva secretion in a SS-like mouse model when applied before disease onset. However, this therapy cannot be used in SS patients given that diagnosis occurs post-disease onset and no reliable screening methods exist. Therefore, we examined whether treatment with AT-RvD1 reduces SS-like features in a mouse model post-disease onset. Methods Tail vein injections were performed in a SS-like mouse model both with and without AT-RvD1 post-disease onset for 8 weeks, with salivary gland function and inflammatory status subsequently determined. Results Treatment of a SS-like mouse model with AT-RvD1 post-disease onset restores saliva secretion in both females and males. Moreover, although AT-RvD1 treatment does not reduce the overall submandibular gland lymphocytic infiltration, it does reduce the number of T helper 17 cells within the infiltrates in both sexes. Finally, AT-RvD1 reduces SS-associated pro-inflammatory cytokine gene and protein expression levels in submandibular glands from female but not male mice. Conclusion AT-RvD1 treatment administered post-disease onset reduces T helper 17 cells and successfully restores salivary gland function in a SS mouse model with variable effects noted by sex, thus warranting further examination of both the causes for the sex differences and the mechanisms responsible for the observed treatment effect.
- Published
- 2018