Expression and Role of the Calcium-Sensing Receptor in Rat Peripheral Blood Polymorphonuclear Neutrophils.

Expression and Role of the Calcium-Sensing Receptor in Rat Peripheral Blood Polymorphonuclear Neutrophils.
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大鼠外周血多形核中性粒细胞钙敏感受体的表达及作用

DOI:
10.1155/2017/3869561
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发表时间:
2017
影响因子:
--
通讯作者:
Sun YH
Sun YH
中科院分区:
生物学2区
文献类型:
--
作者:
Zhai TY;Cui BH;Zou L;Zeng JY;Gao S;Zhao Q;Wang Y;Xie WL;Sun YH

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钙敏感受体(CaSR)在许多参与炎症反应的组织器官中发挥着重要作用。外周血中性粒细胞(PMN)是重要的炎症细胞。然而,有关CaSR在外周血中性粒细胞中的表达和功能的研究尚未见报道。在本研究中,我们采集了大鼠外周血中性粒细胞,观察了CaSR与中性粒细胞的关系。结果发现,CaSR蛋白在中性粒细胞中有表达,经fMLP活化后,CaSR蛋白的表达增强。此外,CaSR激活剂Cincalcet还能促进CaSR、P-κB信号通路蛋白和Bclxl的表达,增加IL-6和髓过氧化物酶的分泌,同时减少促凋亡蛋白bax的表达,减少IL-10和ROS的产生。同时,流式细胞仪分析显示,Cincalcet还能降低PMN凋亡率。然而,CaSR抑制剂NPS-2143和NF-κB信号通路抑制剂PDTC逆转了前面提到的结果。这些结果表明,CaSR可以调节中性粒细胞的功能和状态,从而在炎症中发挥作用,这可能是通过NF-κB信号通路实现的。
The calcium-sensing receptors (CaSRs) play an important role in many tissues and organs that are involved in inflammatory reactions. Peripheral blood polymorphonuclear neutrophils (PMNs) are important inflammatory cells. However, the expression and functions of CaSR in peripheral blood PMNs are still not reported. In this study, we collected rat peripheral blood PMNs to observe the relationship between CaSR and PMNs. From the results, we found first that the CaSR protein was expressed in PMNs, and it increased after PMNs were activated with fMLP. In addition, CaSR activator cincalcet promoted the expression of CaSR and P-p65 (NF-κB signaling pathway protein) and Bcl-xl (antiapoptosis protein), and it increased the secretion of interleukin-6 (IL-6) and myeloperoxidase (MPO); meanwhile, it decreased proapoptosis protein Bax expression and the production of IL-10 and reactive oxygen species (ROS). At the same time, cincalcet also decreased the PMN apoptosis rate analyzed by flow cytometry. However, CaSR inhibitor NPS-2143 and NF-κB signaling pathway inhibitor PDTC reverse the results cited earlier. All of these results indicated that CaSR can regulate PMN functions and status to play a role in inflammation, which is probably through the NF-κB signaling pathway.
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