Expression of the calcium sensing receptor in human peripheral blood T lymphocyte and its contribution to cytokine secretion through MAPKs or NF-κB pathways
Expression of the calcium sensing receptor in human peripheral blood T lymphocyte and its contribution to cytokine secretion through MAPKs or NF-κB pathways
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DOI：
10.1016/j.molimm.2012.09.010
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发表时间：
2013-04-01
影响因子：
3.6
通讯作者：
Sun, Yihua
中科院分区：
文献类型：
--
作者：
Li, Tingting;Sun, Mingrui;Sun, Yihua
钙敏感受体（CaSR）在许多组织和器官中发挥重要作用。然而，关于T淋巴细胞中CaSR的表达和功能的研究还不是很清楚。本研究采用RT-PCR、免疫荧光染色、Western blotting和ELISA等技术对上述问题进行了研究。我们发现正常人外周血T淋巴细胞中有CaSR蛋白的表达，且主要定位于细胞膜上。GdCl 3（CaSR激动剂）增加CaSR表达的剂量依赖性，其被NPS 2390（CaSR抑制剂）消除。GdCl 3和Ca 2+可增加细胞外信号调节激酶（ERK）1/2（MAPKs的一个亚群）和P65（NF-κ B亚基）的磷酸化，但对JNK和P38 MAPKs亚群无明显影响。同时，GdCl 3和Ca 2+刺激IL-6和TNF-β的释放及其mRNA表达。然而，GdCl 3和Ca 2+的这些作用被NPS 2390、U 0126（MAPKs通路抑制剂）或Bay-11-7082（NF-κ B通路抑制剂）抑制。这些结果表明，CaSR在T细胞中有功能性表达，活化后的CaSR通过部分MAPK和NF-κ B途径参与细胞因子的分泌。(c)2012爱思唯尔有限公司保留所有权利。
The calcium-sensing receptor (CaSR) has been reported to play an important role in many tissues and organs. However, studies about the expression and function of CaSR in T lymphocytes are still not very lucid. In this study, we investigated the above-mentioned issues using RT-PCR, immunofluorescence staining, Western blotting, and the ELISA techniques. We found that the CaSR protein was expressed, and mainly located in the membrane in the normal human peripheral blood T lymphocytes. GdCl3 (an agonist of CaSR) increased the dose-dependency of the CaSR expression, which was abolished by NPS2390 (an inhibitor of CaSR). GdCl3 and Ca2+ increased the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 (one subgroup of MAPKs) and P65 (subunit of NF-kappa B),but, they had no significant effects on the JNK and P38 subgroups of MAPKs. Meantime, GdCl3 and Ca2+ stimulated both the IL-6 and TNF-beta releases and their mRNA expressions. However, these effects of GdCl3 and Ca2+ were inhibited by NPS2390, U0126 (MAPKs pathway inhibitor) or Bay-11-7082 (NF-kappa B pathway inhibitor). These results suggested that CaSR was functionally expressed in the T cells, and the activated CaSR contributed to the cytokine secretion through the partial MAPK and NF-kappa B pathways. (c) 2012 Elsevier Ltd. All rights reserved.