Neochromine S5 improves contact hypersensitivity through a selective effect on activated T lymphocytes
Neochromine S5 improves contact hypersensitivity through a selective effect on activated T lymphocytes
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Neochromine S5 通过对活化 T 淋巴细胞的选择性作用改善接触超敏反应
DOI：
10.1016/j.bcp.2014.08.032
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发表时间：
2014-11-15
影响因子：
5.8
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Gao, Zhe;Ma, Yuxiang;Xu, Qiang
激活T细胞的策略是治疗T细胞介导的疾病的有效方法。通过使用合成的色酮衍生物，我们研究了其对活化的T细胞的影响。该化合物（Z）-1，3-二羟基-9-甲基-1，3 H-苯并[B]色烯并[3，2-f][1，4]氧氮杂卓-13-酮（neochromine S5）在体外和体内均表现出免疫抑制活性。有趣的是，新色胺S5选择性地抑制增殖和诱导凋亡的伴刀豆球蛋白A（刀豆球蛋白A）激活的T淋巴细胞在剂量依赖性的方式，但不是在幼稚T淋巴细胞，不同的槲皮素。该化合物在活化的T细胞中触发线粒体凋亡途径，包括caspase 3、caspase 9和PARP的裂解，bc 1 -2的下调和细胞色素c的释放，但不影响ER应激或Fas信号。此外，新色胺S5下调CD 25和CD 69的表达以及炎性细胞因子（包括TNF α、IFN-γ和IL-2）的产生，改善接触性超敏反应小鼠的耳肿胀，减少CD 4（+）T细胞浸润，并增加外周淋巴结分离的T淋巴细胞的凋亡。此外，新色胺S5对小鼠及其免疫器官的重量没有影响，而地塞米松引起了显着的体重减轻。总之，我们的结果表明，新色胺S5主要通过对活化的T细胞的选择性作用发挥独特的抗炎活性which.is不同于目前的免疫抑制剂地塞米松。(C)2014爱思唯尔公司All rights reserved.
Strategy on activated T cells is an effective treatment for T cell mediated diseases. By using a synthesized chromone derivative, we examined its effects on the activated T cells. This compound, (Z)-1,3-dihydroxy-9-methyl-1,3H-benzo[b]chromeno[3,2-f][1,4]oxazepin-13-one (neochromine S5), exhibited immunosuppressive activity in vitro and in vivo. Interestingly, neochromine S5 selectively inhibited proliferation and induced apoptosis in T lymphocytes activated by concanavalin A (Con A) in a dose-dependent manner but not in naive T lymphocytes, distinct from quercetin. This compound triggered mitochondrial apoptotic pathway including cleavage of caspase 3, caspase 9 and PARP, downregulation of bc1-2 and release of cytochrome c in activated T cells, but did not affect ER stress or Fas signals. In addition, neochromine S5 downregulated the expression of CD25 and CD69 and the production of inflammatory cytokines, including TNF alpha, IFN-gamma and IL-2, improved ear swelling in mice with contact hypersensitivity, reduced CD4(+) T cells infiltration, and increased apoptosis of isolated T lymphocytes from peripheral lymph nodes. Moreover, neochromine S5 showed no effect on the weight of mice and their immune organs, while dexamethasone caused a significant weight loss. Taken together, our results suggest that neochromine S5 exerts a unique anti-inflammatory activity mainly through a selective effect on.activated T cells, which.is different from the current immunosuppressant, dexamethasone. (C) 2014 Elsevier Inc. All rights reserved.