Orai1 downregulation impairs lymphocyte function in type 2 diabetes mellitus
Orai1 downregulation impairs lymphocyte function in type 2 diabetes mellitus
复制标题
Orai1 下调损害 2 型糖尿病患者的淋巴细胞功能
DOI：
10.1016/j.bbrc.2018.04.083
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发表时间：
2018
影响因子：
3.1
通讯作者：
Luo Dali
中科院分区：
文献类型：
--
作者：
Wang Haoyang;Wang Cong;Wang Limin;Liu Tiantian;Wang Zhigiang;You Hongjie;Zheng Yuanyuan;Luo Dali
背景/目的糖尿病与免疫功能紊乱有关，其中淋巴细胞内Ca ~（2+）信号传导障碍可能起主要作用。然而，Ca 2+信号紊乱的模式和解释这种变化的机制尚不清楚。在这里，在这项研究中，我们的目的是调查可能的变化和机制（S）占糖尿病T淋巴细胞的内部Ca 2+信号在stimulation.Methods和resultsUsing Fura-2-AM，我们发现了显着减少由毒胡萝卜素（TG）和抗CD 3抗体（OKT 3）诱导的糖尿病患者和动物的血液中的T淋巴细胞内流。此外，下调Orai 1蛋白的表达，但不是mRNA，也观察到在这些细胞中，分别使用western blot和qRT-PCR。此外，在高糖和激动剂处理的Jurkat T细胞中，Ca 2+内流和白细胞介素-2（IL-2）的释放也减少。Orai 1表达减少，而基质相互作用分子1（STIM 1）和其他下游蛋白保持不变conclusionThis研究表明，下降Orai 1的表达，至少部分，有助于下调钙离子进入淋巴细胞兴奋过程中，提供了一个重要的机制，T淋巴细胞功能障碍在糖尿病。
Background/AimsIt has been suggested that diabetes is associated with immune dysfunction, in which Ca2+signaling malfunction in lymphocyte may contributes most. However, the pattern of the Ca2+signal disorder and the mechanism(s) that explains the change are unclear. Here, in this study we aimed to investigate possible changes and mechanism(s) accounting for the internal Ca2+signals in diabetic T lymphocyte upon stimulation.Methods and resultsUsing Fura-2-AM, we found a significant decrease in Ca2+influx induced by thapsigargin (TG) and anti-CD3 antibody (OKT3) in T lymphocytes from blood of both diabetes patients and animals. Furthermore, a downregulated Orai1 protein expression, but not mRNA, was also observed in these cells using western blot and qRT-PCR, respectively. In addition, in high-glucose and agonist treated Jurkat T cells, Ca2+entry and the release of interleukin-2 (IL-2) were also decreased. Orai1 expression reduced, while stromal interaction molecule 1 (STIM1) and other downstream proteins remained unchanged.ConclusionThis study demonstrates that the declined Orai1 expression, at least partly, contributes to the downregulated Ca2+entry during lymphocyte excitation, providing an important mechanism for T lymphocyte malfunction in diabetes.