Activation of α7 nicotinic acetylcholine receptors attenuates monocyte endothelial adhesion through FUT7 inhibition
Activation of α7 nicotinic acetylcholine receptors attenuates monocyte endothelial adhesion through FUT7 inhibition
复制标题
α7 烟碱乙酰胆碱受体的激活通过抑制 FUT7 减弱单核细胞内皮粘附
DOI：
10.1016/j.bbrc.2021.12.094
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发表时间：
2022
影响因子：
3.1
通讯作者：
Inagi Reiko
中科院分区：
文献类型：
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作者：
Wu Chia-Hsien;Inoue Tsuyoshi;Nakamura Yasuna;Uni Rie;Hasegawa Sho;Maekawa Hiroshi;Sugahara Mai;Wada Youichiro;Tanaka Tetsuhiro;Nangaku Masaomi;Inagi Reiko
胆碱能抗炎通路 (CAP) 描述了一种神经元炎症反射，其集中于通过脾残留巨噬细胞的 α7 烟碱乙酰胆碱受体 (α7nAChR) 激活的全身细胞因子调节。然而，CAP 减轻远端组织炎症、诱导低水平全身炎症的机制却鲜为人知。在这项研究中，我们假设 CAP 通过影响单核细胞与内皮细胞的粘附来调节单核细胞的可及性。通过 RNA-seq 分析，我们发现 α1,3-岩藻糖基转移酶 7 (FucT-VII)（加工选择素配体所需的酶）在其他细胞-细胞粘附基因中被 α7nAChR 激动剂显着下调。 α7nAChR 激动剂抑制单核细胞系 U-937 与 P-选择素的结合以及与内皮细胞的粘附。此外，通过α7nAChR敲低测定证实了α7nAChR激动剂选择性，表明针对α7nAChR编码基因的siRNA消除了激动剂对FUT7的抑制和粘附减弱。一致地，FUT7 敲低抑制了 U-937 的粘附特性并阻止它们粘附到内皮细胞。 FUT7 的过表达还消除了 GTS-21 诱导的粘附减弱，表明 FUT7 抑制足以通过 α7nAChR 激活抑制粘附。我们的工作表明，α7nAChR 激活通过 FUT7 抑制调节单核细胞与内皮细胞的粘附，为 CAP 机制提供了新的见解。
Cholinergic anti-inflammatory pathway (CAP) describes a neuronal-inflammatory reflex centered on systemic cytokine regulation by α7 nicotinic acetylcholine receptor (α7nAChR) activation of spleen-residue macrophage. However, the CAP mechanism attenuating distal tissue inflammation, inducing a low level of systemic inflammation, is lesser known. In this study, we hypothesized that CAP regulates monocyte accessibility by influencing their adhesion to endothelial cells. Using RNA-seq analysis, we identified that α1,3-Fucosyltransferase 7 (FucT-VII), the enzyme required for processing selectin ligands, was significantly downregulated by α7nAChR agonist among other cell–cell adhesion genes. The α7nAChR agonist inhibited monocytic cell line U-937 binding to P-selectin and adhesion to endothelial cells. Furthermore, α7nAChR agonist selectivity was confirmed by α7nAChR knockdown assays, showing thatFUT7inhibition and adhesion attenuation by the agonist was abolished by siRNA targeting α7nAChR encoding gene. Consistently,FUT7knockdown inhibited the adhesive properties of U-937 and prevented them to adhere to endothelial cells. Overexpression ofFUT7also abrogated the adhesion attenuation induced by GTS-21 indicating thatFUT7inhibition was sufficient for inhibiting adhesion by α7nAChR activation. Our work demonstrated that α7nAChR activation regulates monocyte adhesion to endothelial cells throughFUT7inhibition, providing a novel insight into the CAP mechanism.