Aspirin Triggered Resolvin D1 reduces inflammation and restores saliva secretion in a Sjogren's syndrome mouse model
Aspirin Triggered Resolvin D1 reduces inflammation and restores saliva secretion in a Sjogren's syndrome mouse model
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DOI：
10.1093/rheumatology/kez072
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发表时间：
2019-07-01
期刊：
影响因子：
5.5
通讯作者：
Baker, Olga J.
中科院分区：
文献类型：
--
作者：
Dean, Spencer;Wang, Ching-Shuen;Baker, Olga J.
目的SS的特点是慢性炎症的唾液腺导致分泌功能的丧失，从而表明专门的前解决介质针对炎症是一个可行的选择治疗SS。先前的研究表明，阿司匹林触发的消退素D1（AT-RvD 1）在疾病发作前应用时可预防SS样小鼠模型中的慢性炎症并增强唾液分泌。然而，这种疗法不能用于SS患者，因为诊断发生在疾病发作后，并且不存在可靠的筛查方法。因此，我们研究了用AT-RvD 1治疗是否减少疾病发作后小鼠模型中的SS样特征。方法在疾病发作后8周内，在有和没有AT-RvD 1的SS样小鼠模型中进行尾静脉注射，随后测定唾液腺功能和炎症状态。疾病发作恢复了女性和男性的唾液分泌。此外，虽然AT-RvD 1治疗并没有减少整体颌下腺淋巴细胞浸润，但它确实减少了两种性别浸润物中T辅助细胞17的数量。最后，AT-RvD 1降低SS相关的促炎细胞因子基因和蛋白表达水平，在雌性小鼠的下颌下腺，而不是男性。结论AT-RvD 1治疗后，疾病发作减少T辅助细胞17细胞，并成功地恢复唾液腺功能，在SS小鼠模型中，因此，需要进一步研究性别差异的原因和观察到的治疗效果的机制。
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.