ALX/FPR2 Modulates Anti-Inflammatory Responses in Mouse Submandibular Gland.
ALX/FPR2 Modulates Anti-Inflammatory Responses in Mouse Submandibular Gland.
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DOI：
10.1038/srep24244
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发表时间：
2016-04-11
影响因子：
4.6
通讯作者：
Baker OJ
中科院分区：
文献类型：
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作者：
Wang CS;Wee Y;Yang CH;Melvin JE;Baker OJ
G蛋白偶联甲酰肽受体2(ALX/FPR2)被脂类介体脂氧素A4和分解蛋白D 1(RvD 1)激活，促进炎症消退。我们之前的体外研究表明，ALX/FPR2的RvD1激活可以解决哺乳动物细胞中细胞因子介导的炎症反应。然而，体内ALX/FPR2激活对唾液腺功能的影响尚不清楚。本研究的目的是确定ALx/Fpr2−/−小鼠颌下腺对内毒素刺激的炎症反应是否增强。对8~12周龄的C57BL/6和ALX/FPR2−/−小鼠给予脂多糖治疗24 h，通过组织病理学、唾液流率、定量聚合酶链式反应、Western印迹分析和免疫荧光等方法分析唾液腺的结构和功能。结果表明，−/−小鼠经脂多糖治疗后，炎症细胞因子表达上调，M3R(M受体M3)和AQP5(水通道蛋白5)蛋白表达减少，唾液分泌减少，细胞凋亡率增加，紧密连接改变，神经元损伤。总体而言，我们的数据表明，ALX/FPR2的缺失会导致急性炎症和SMG功能障碍(口干症)无法解决，这类似于细菌感染导致的人类唾液腺功能障碍。
Activation of the G-protein coupled formyl peptide receptor 2 (ALX/FPR2) by the lipid mediators lipoxin A4 and resolvin D1 (RvD1) promotes resolution of inflammation. Our previous in vitro studies indicate that RvD1 activation of ALX/FPR2 resolves cytokine-mediated inflammatory responses in mammalian cells. However, the impact of ALX/FPR2 activation on salivary gland function in vivo is unknown. The objective of this study was to determine whether submandibular glands (SMG) from ALX/FPR2−/− mice display enhanced inflammatory responses to lipopolysaccharides (LPS) stimulation. For these studies, C57BL/6 and ALX/FPR2−/− mice at age 8-12-week-old were treated with LPS by i.p for 24 h. Salivary gland structure and function were analyzed by histopathological assessment, saliva flow rate, quantitative PCR, Western blot analyses and immunofluorescence. Our results showed the following events in the ALX/FPR2−/− mice treated with LPS: a) upregulated inflammatory cytokines and decreased M3R (Muscarinic Acetylcholine receptor M3) and AQP5 (Aquaporin 5) protein expression, b) decreased saliva secretion, c) increased apoptosis, d) alteration of tight junction and neuronal damage. Overall, our data suggest that the loss of ALX/FPR2 results in unresolved acute inflammation and SMG dysfunction (xerostomia) in response to LPS that is similar to human salivary gland dysfunction induced by bacterial infection.