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钙敏感受体在大鼠外周血多形核中性粒细胞中的表达及作用。

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

机构信息

Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin 150086, China.

出版信息

Oxid Med Cell Longev. 2017;2017:3869561. doi: 10.1155/2017/3869561. Epub 2017 Sep 10.

Abstract

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-B 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-B 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-B signaling pathway.

摘要

钙敏感受体(CaSRs)在涉及炎症反应的许多组织和器官中发挥重要作用。外周血多形核粒细胞(PMNs)是重要的炎症细胞。然而,外周血 PMNs 中 CaSR 的表达和功能仍未见报道。在这项研究中,我们收集了大鼠外周血 PMNs,以观察 CaSR 与 PMNs 之间的关系。结果发现,首先,CaSR 蛋白在外周血 PMNs 中表达,并且在用 fMLP 激活 PMNs 后增加。此外,CaSR 激动剂西那卡塞促进 CaSR 和 P-p65(NF-B 信号通路蛋白)和 Bcl-xl(抗凋亡蛋白)的表达,并增加白细胞介素-6(IL-6)和髓过氧化物酶(MPO)的分泌;同时,它降低了促凋亡蛋白 Bax 的表达和 IL-10 和活性氧(ROS)的产生。同时,流式细胞术分析也表明西那卡塞还降低了 PMN 的凋亡率。然而,CaSR 抑制剂 NPS-2143 和 NF-B 信号通路抑制剂 PDTC 逆转了上述结果。所有这些结果表明,CaSR 可以调节 PMN 的功能和状态,在炎症中发挥作用,这可能是通过 NF-B 信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2308/5610836/b84a8417dbbd/OMCL2017-3869561.001.jpg

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