Increased expression and functionality of the gap junction in peripheral blood lymphocytes is associated with hypertension-mediated inflammation in spontaneously hypertensive rats.
Increased expression and functionality of the gap junction in peripheral blood lymphocytes is associated with hypertension-mediated inflammation in spontaneously hypertensive rats.
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自发性高血压大鼠外周血淋巴细胞间隙连接表达和功能的增加与高血压介导的炎症相关
DOI：
10.1186/s11658-018-0106-0
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发表时间：
2018
影响因子：
8.3
通讯作者：
Ma KT
中科院分区：
文献类型：
--
作者：
Ni X;Li XZ;Fan ZR;Wang A;Zhang HC;Zhang L;Li L;Si JQ;Ma KT
循环T淋巴细胞失衡在高血压介导的炎症发病机制中起重要作用。免疫细胞中的缝隙连接蛋白(CXS)参与T淋巴细胞内稳态的维持。然而，外周血T淋巴细胞中的CXS与高血压介导的炎症之间的联系仍不清楚。本研究旨在探讨CXS在自发性高血压大鼠(SHR)高血压介导的炎症反应中的作用。采用尾套法对Wistar-京都(WKY)大鼠和自发性高血压大鼠的收缩压(SBP)进行监测。采用双抗体夹心法测定血清细胞因子水平。用流式细胞仪检测外周血中不同T淋巴细胞亚群比例、T细胞亚群中Cx40/Cx43的表达以及外周血淋巴细胞缝隙连接细胞内通讯(GJIC)。免疫荧光染色检测Cx40/Cx43在细胞膜和/或胞浆中的积聚。用荧光定量聚合酶链式反应和荧光抗体分别检测经Gap27和/或刀豆蛋白A(ConA)处理后外周血淋巴细胞中细胞因子和GJIC基因的表达水平。SHR大鼠外周血中CD_4~+T细胞百分率和CD_4~+/CD_8~+比值均高于WKY大鼠，外周血淋巴细胞中Cx40/Cx43的积聚或表达均高于WKY大鼠。SHR患者外周血中CD8+、CD4+CD25+T细胞百分率较低。SHR大鼠血清IL-2、IL-4、IL-6水平均高于WKY大鼠，且SHR血清IL-2、IL-6水平与外周血T淋巴细胞Cx40/Cx43表达呈正相关。SHR的外周血淋巴细胞GJIC增强。由Gap27介导的基于Cx43的通道抑制可显著降低淋巴细胞GJIC，并抑制ConA刺激的外周血淋巴细胞IL-2和IL-6mRNA的表达。我们的数据提示CXS可能参与调节T淋巴细胞的动态平衡和细胞因子的产生。在CXS表达的改变或基于Cx43的GJIC与高血压介导的炎症之间发现了明显的关联。
Imbalances in circulating T lymphocytes play critical roles in the pathogenesis of hypertension-mediated inflammation. Connexins (Cxs) in immune cells are involved in the maintenance of homeostasis of T lymphocytes. However, the association between Cxs in peripheral blood T lymphocytes and hypertension-mediated inflammation remains unknown. This study was designed to investigate the role of Cxs in T lymphocytes in hypertension-mediated inflammation in spontaneously hypertensive rats (SHRs). The systolic blood pressure (SBP) in Wistar-Kyoto (WKY) rats and SHRs was monitored using the tail-cuff method. The serum cytokine level was determined using ELISA. The proportions of different T-lymphocyte subtypes in the peripheral blood, the expressions of Cx40/Cx43 in the T-cell subtypes, and the gap junctional intracellular communication (GJIC) of peripheral blood lymphocytes were measured using flow cytometry (FC). The accumulations of Cx40/Cx43 at the plasma membrane and/or in the cytoplasm were determined using immunofluorescence staining. The in vitro mRNA levels of cytokines and GJIC in the peripheral blood lymphocytes were respectively examined using real-time PCR and FC after treatment with Gap27 and/or concanavalin A (Con A). The percentage of CD4+ T cells and the CD4+/CD8+ ratio were high, and the accumulation or expressions of Cx40/Cx43 in the peripheral blood lymphocytes in SHRs were higher than in those of WKY rats. The percentage of CD8+ and CD4+CD25+ T cells was lower in SHRs. The serum levels of IL-2, IL-4 and IL-6 from SHRs were higher than those from WKY rats, and the serum levels of IL-2 and IL-6 positively correlated with the expression of Cx40/Cx43 in the peripheral blood T lymphocytes from SHRs. The peripheral blood lymphocytes of SHRs exhibited enhanced GJIC. Cx43-based channel inhibition, which was mediated by Gap27, remarkably reduced GJIC in lymphocytes, and suppressed IL-2 and IL-6 mRNA expressions in Con A stimulated peripheral blood lymphocytes. Our data suggest that Cxs may be involved in the regulation of T-lymphocyte homeostasis and the production of cytokines. A clear association was found between alterations in Cxs expression or in Cx43-based GJIC and hypertension-mediated inflammation.
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