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Piezo1 在人嗜酸性粒细胞细胞系 AML14.3D10 中的功能作用:对免疫和感觉神经系统的影响。

Functional Role of Piezo1 in the Human Eosinophil Cell Line AML14.3D10: Implications for the Immune and Sensory Nervous Systems.

机构信息

Gachon Pain Center and Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Republic of Korea.

Department of Health Science and Technology, Gachon Advanced Institute for Health Science & Technology, Gachon University, Incheon 21999, Republic of Korea.

出版信息

Biomolecules. 2024 Sep 14;14(9):1157. doi: 10.3390/biom14091157.

Abstract

Mechanosensitive ion channels, particularly Piezo channels, are widely expressed in various tissues. However, their role in immune cells remains underexplored. Therefore, this study aimed to investigate the functional role of Piezo1 in the human eosinophil cell line AML14.3D10. We detected mRNA expression, but not expression, in these cells, confirming the presence of the Piezo1 protein. Activation of Piezo1 with Yoda1, its specific agonist, resulted in a significant calcium influx, which was inhibited by the Piezo1-specific inhibitor Dooku1, as well as other nonspecific inhibitors (Ruthenium Red, Gd, and GsMTx-4). Further analysis revealed that Piezo1 activation modulated the expression and secretion of both pro-inflammatory and anti-inflammatory cytokines in AML14.3D10 cells. Notably, supernatants from Piezo1-activated AML14.3D10 cells enhanced capsaicin and ATP-induced calcium responses in the dorsal root ganglion neurons of mice. These findings elucidate the physiological role of Piezo1 in AML14.3D10 cells and suggest that factors secreted by these cells can modulate the activity of transient receptor potential 1 (TRPV1) and purinergic receptors, which are associated with pain and itch signaling. The results of this study significantly advance our understanding of the function of Piezo1 channels in the immune and sensory nervous systems.

摘要

机械敏感性离子通道,特别是 Piezo 通道,广泛表达于各种组织中。然而,它们在免疫细胞中的作用仍未被充分探索。因此,本研究旨在探究 Piezo1 在人嗜酸性粒细胞系 AML14.3D10 中的功能作用。我们检测到这些细胞中存在 Piezo1 的 mRNA 表达,但不存在 Piezo1 的蛋白表达,证实了 Piezo1 蛋白的存在。Piezo1 的激活剂 Yoda1 引起了显著的钙离子内流,该过程可被 Piezo1 特异性抑制剂 Dooku1 以及其他非特异性抑制剂(钌红、Gd 和 GsMTx-4)所抑制。进一步的分析表明,Piezo1 的激活调节了 AML14.3D10 细胞中促炎和抗炎细胞因子的表达和分泌。值得注意的是,Piezo1 激活后的 AML14.3D10 细胞上清液增强了小鼠背根神经节神经元中辣椒素和 ATP 诱导的钙离子反应。这些发现阐明了 Piezo1 在 AML14.3D10 细胞中的生理作用,并提示这些细胞分泌的因子可以调节瞬时受体电位 1(TRPV1)和嘌呤能受体的活性,而 TRPV1 和嘌呤能受体与疼痛和瘙痒信号转导有关。本研究的结果显著推进了我们对 Piezo1 通道在免疫和感觉神经系统中的功能的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1825/11429562/c3d70b133ac1/biomolecules-14-01157-g001.jpg

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