Anhui Province Key Laboratory of Local Livestock and Poultry Genetic Resource Conservation and Bio-breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, China.
Anhui Province Key Laboratory of Local Livestock and Poultry Genetic Resource Conservation and Bio-breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, China.
Dev Comp Immunol. 2022 Mar;128:104328. doi: 10.1016/j.dci.2021.104328. Epub 2021 Dec 6.
N-acetylcholine receptors (AChRs) are mainly distributed in the postsynaptic membrane and have been widely studied for their control of muscle contraction by regulating neural action potentials. However, the influences of AChRs on immune responses and potential mechanisms remain unclear. Here, we used the advantages of live imaging of zebrafish to explore the regulation process of AChRs on inflammatory responses. Pharmacologically activating of the receptor, we found that the expression of pro-inflammatory cytokines il-1β, il-6, tnf-α and il-8 was significantly up-regulated and neutrophil migration to injury sites was also significantly increased. However, these phenomena were reversed under antagonism of the receptor activity. Results showed that interfering with nAChRs functions did not significantly affect zebrafish motion behavior. Results also showed that activation and antagonism of nAChRs function could regulate the phosphorylation of ERK protein respectively. We further demonstrated that ERK participated in the regulation of AChRs in cytokines expression and neutrophils migration in zebrafish. This study preliminarily revealed the roles of AChRs in inflammatory processes and their potential mechanism, providing additional evidence of peripheral immune regulation by cholinergic receptors.
N-乙酰胆碱受体 (AChRs) 主要分布在突触后膜，通过调节神经动作电位来控制肌肉收缩，其功能已得到广泛研究。然而，AChRs 对免疫反应的影响及其潜在机制仍不清楚。在这里，我们利用斑马鱼活体成像的优势，探索了 AChRs 对炎症反应的调节过程。通过药理学激活该受体，我们发现促炎细胞因子 il-1β、il-6、tnf-α 和 il-8 的表达显著上调，中性粒细胞向损伤部位的迁移也显著增加。然而，在拮抗该受体活性的情况下，这些现象被逆转。结果表明，干扰 nAChRs 的功能对斑马鱼的运动行为没有显著影响。结果还表明，激活和拮抗 nAChRs 功能可以分别调节 ERK 蛋白的磷酸化。我们进一步证明 ERK 参与了 AChRs 在斑马鱼细胞因子表达和中性粒细胞迁移中的调节作用。本研究初步揭示了 AChRs 在炎症过程中的作用及其潜在机制，为胆碱能受体对周围免疫系统的调节提供了额外的证据。
