Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Shinjuku-ku, Tokyo, 162-8480, Japan.
Waseda Institute for Advanced Study, Waseda University, 1-6-1 Nishi-Waseda, Shinjuku-ku, Tokyo, 169-8050, Japan.
Sci Rep. 2017 Aug 18;7(1):8802. doi: 10.1038/s41598-017-09438-0.
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.
唾液腺受来自视交叉上核(SCN)的交感神经激活的节律性控制,SCN 作为昼夜节律的主要振荡器。在人类中,唾液 IgA 浓度反映了昼夜节律性,在睡眠期间达到峰值。然而,控制这种节律性的机制尚不清楚。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)激活的时间是否会影响唾液中的 IgA 分泌。毛果芸香碱激活或毛果芸香碱和 NE 联合激活调节的唾液 IgA 浓度在光周期中期最高,与唾液流速无关。SCN 损伤和 Clock 基因突变削弱了 IgA 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了 NE 和毛果芸香碱诱导的 IgA 基础分泌。二聚体 IgA 结合到上皮细胞基底外侧表面的多聚免疫球蛋白受体(pIgR)上,并形成 IgA-pIgR 复合物。Pigr 丰度的昼夜节律在光周期期间达到峰值,表明 IgA 节律性分泌时 pIgR 的表达。我们推测,睡眠期间交感神经的激活可能通过增强 IgA 的分泌来防止细菌进入上皮表面。