Induction of tetraspanin 13 contributes to the synergistic anti-inflammatory effects of parasympathetic and sympathetic stimulation in macrophages
Induction of tetraspanin 13 contributes to the synergistic anti-inflammatory effects of parasympathetic and sympathetic stimulation in macrophages
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DOI：
10.1016/j.bbrc.2023.04.118
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发表时间：
2023-05-08
影响因子：
3.1
通讯作者：
Inoue，Tsuyoshi
中科院分区：
文献类型：
--
作者：
Umene，Ryusuke;Nakamura，Yasuna;Inoue，Tsuyoshi
自主神经系统在外周炎症的调节中起重要作用。交感神经激活刺激炎性基因表达和细胞因子，而副交感神经激活抑制免疫细胞产生炎性细胞因子。然而，大多数关于自主神经系统和免疫过程之间关系的研究都是孤立地分析了自主神经的单个分支。因此，本研究旨在观察交感神经和副交感神经刺激对巨噬细胞的影响，巨噬细胞受自主神经调节的控制。然后，使用浓度依赖性测定评估β2肾上腺素能受体和α7烟碱乙酰胆碱受体激活对TNF-α产生的影响。同时激活β2肾上腺素能受体和α7烟碱乙酰胆碱受体以浓度依赖性方式抑制LPS诱导的TNF-α产生。此外，这些受体的同时激活具有协同抗炎作用，并诱导Tspan 13的表达，从而有助于巨噬细胞的抗炎机制。我们的研究结果表明，靶向交感神经和副交感神经信号传导是一种有前途的治疗炎症性疾病的方法。
The autonomic nervous system plays an important role in the regulation of peripheral inflammation. Sympathetic nervous activation stimulates inflammatory gene expression and cytokines, whereas parasympathetic nervous activation suppresses the production of inflammatory cytokines by immune cells. However, most studies on the relationship between the autonomic nervous system and immune processes have analyzed a single branch of the autonomic nerves in isolation. Therefore, this study aimed to examine the effects of sympathetic and parasympathetic stimulation on macrophages, which are controlled by autonomic regulation.Macrophages were stimulated with lipopolysaccharide (LPS) to induce TNF-α. Then, the effects of β2 adrenergic receptor and α7 nicotinic acetylcholine receptor activation on TNF-α production were assessed using concentration-dependent assays. RNA-seq data were also used to identify genes whose expression was enhanced by parasympathetic and sympathetic stimulation.The simultaneous activation of β2 adrenergic receptors and α7 nicotinic acetylcholine receptors suppressed LPS-induced TNF-α production in a concentration-dependent manner. Moreover, simultaneous activation of these receptors had synergistic anti-inflammatory effects and inducedTspan13expression, thereby contributing to anti-inflammatory mechanisms in macrophages.Our study revealed the synergistic anti-inflammatory effects of the parasympathetic and sympathetic stimulation of macrophages. Our results suggest that targeting both sympathetic and parasympathetic signaling is a promising therapeutic approach for inflammatory diseases.