Department of Pharmacology, Huazhong University of Science and Technology, Wuhan, 430030, China.
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Huazhong University of Science and Technology, Wuhan, 430030, China.
Curr Med Sci. 2018 Jun;38(3):436-442. doi: 10.1007/s11596-018-1897-y. Epub 2018 Jun 22.
Activation of acid-sensing ion channels (ASICs) plays an important role in neuroinflammation. Macrophage recruitment to the sites of inflammation is an essential step in host defense. ASIC1 and ASIC3 have been reported to mediate the endocytosis and maturation of bone marrow derived macrophages. However, the expression and inflammation-related functions of ASICs in RAW 264.7 cells, another common macrophage, are still elusive. In the present study, we first demonstrated the presence of ASIC1, ASIC2a and ASIC3 in RAW 264.7 macrophage cell line by using reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence experiments. The non-specific ASICs inhibitor amiloride and specific homomeric ASICla blocker PcTxl reduced the production of iNOS and COX-2 by LPS-induced activating RAW 264.7 cells. Furthermore, not only amiloride but also PcTxl inhibited the migration and LPS-induced apoptosis of RAW 264.7 cells. Taken together, our findings suggest that ASICs promote the inflammatory response and apoptosis of RAW 264.7 cells, and ASICs may serve as a potential novel target for immunological disease therapy.
酸敏离子通道 (ASICs) 的激活在神经炎症中发挥重要作用。巨噬细胞向炎症部位的募集是宿主防御的一个重要步骤。已经报道 ASIC1 和 ASIC3 介导骨髓来源的巨噬细胞的内吞作用和成熟。然而,ASICs 在另一种常见的巨噬细胞 RAW 264.7 细胞中的表达和与炎症相关的功能仍然难以捉摸。在本研究中,我们首先通过逆转录聚合酶链反应 (RT-PCR)、Western blot 和免疫荧光实验证实了 ASIC1、ASIC2a 和 ASIC3 在 RAW 264.7 巨噬细胞系中的存在。非特异性 ASICs 抑制剂阿米洛利和特异性同型 ASICla 阻滞剂 PcTxl 降低了 LPS 诱导的 RAW 264.7 细胞激活产生的 iNOS 和 COX-2。此外,不仅阿米洛利,而且 PcTxl 抑制了 RAW 264.7 细胞的迁移和 LPS 诱导的凋亡。总之,我们的研究结果表明 ASICs 促进 RAW 264.7 细胞的炎症反应和凋亡,ASICs 可能成为免疫性疾病治疗的一个潜在新靶点。