Circadian clock-dependent increase in salivary IgA secretion modulated by sympathetic receptor activation in mice.

Circadian clock-dependent increase in salivary IgA secretion modulated by sympathetic receptor activation in mice.
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DOI:
10.1038/s41598-017-09438-0
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发表时间:
2017-08-18
期刊:
影响因子:
4.6
通讯作者:
Shibata S
Shibata S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wada M;Orihara K;Kamagata M;Hama K;Sasaki H;Haraguchi A;Miyakawa H;Nakao A;Shibata S

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唾液腺由来自视交叉上核(SCN)的交感神经激活有节奏地控制,视交叉上核作为昼夜节律的主要振荡器。在人类中,唾液伊加浓度反映了昼夜节律,在睡眠期间达到峰值。然而,控制这种节律性的机制还不清楚。因此,我们研究了副交感神经(毛果芸香碱)或交感神经(去甲肾上腺素; NE)激活的时间是否影响唾液中的伊加分泌。由毛果芸香碱激活或由毛果芸香碱和NE激活的组合调制的唾液伊加的浓度在光周期的中间是最高的,独立于唾液流速。SCN病变和Clock基因突变减弱了伊加分泌的昼夜节律,表明SCN和Clock基因对这种节律的重要性。肾上腺素能受体拮抗剂阻断NE和毛果芸香碱诱导的伊加基础分泌。二聚体伊加与上皮细胞基底外侧表面上的多聚免疫球蛋白受体(pIgR)结合并形成IgA-pIgR复合物。Pigr丰度的昼夜节律在光照期达到峰值,表明pIgR表达取决于伊加的节律性分泌。我们推测,睡眠期间交感神经的激活可能通过增强伊加的分泌来防止细菌进入上皮表面。
The salivary gland is rhythmically controlled by sympathetic nerve activation from the suprachiasmatic nucleus (SCN), which functions as the main oscillator of circadian rhythms. In humans, salivary IgA concentrations reflect circadian rhythmicity, which peak during sleep. However, the mechanisms controlling this rhythmicity are not well understood. Therefore, we examined whether the timing of parasympathetic (pilocarpine) or sympathetic (norepinephrine; NE) activation affects IgA secretion in the saliva. The concentrations of saliva IgA modulated by pilocarpine activation or by a combination of pilocarpine and NE activation were the highest in the middle of the light period, independent of saliva flow rate. The circadian rhythm of IgA secretion was weakened by an SCN lesion and Clock gene mutation, suggesting the importance of the SCN and Clock gene on this rhythm. Adrenoceptor antagonists blocked both NE- and pilocarpine-induced basal secretion of IgA. Dimeric IgA binds to the polymeric immunoglobulin receptor (pIgR) on the basolateral surface of epithelial cells and forms the IgA-pIgR complex. The circadian rhythm of Pigr abundance peaked during the light period, suggesting pIgR expression upon rhythmic secretion of IgA. We speculate that activation of sympathetic nerves during sleep may protect from bacterial access to the epithelial surface through enhanced secretion of IgA.
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