Cutting edge:: CpG DNA inhibits dendritic cell apoptosis by up-regulating cellular inhibitor of apoptosis proteins through the phosphatidylinositide-3′-OH kinase pathway
Cutting edge:: CpG DNA inhibits dendritic cell apoptosis by up-regulating cellular inhibitor of apoptosis proteins through the phosphatidylinositide-3′-OH kinase pathway
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DOI：
10.4049/jimmunol.168.1.5
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发表时间：
2002-01-01
影响因子：
4.4
通讯作者：
Sung, YC
中科院分区：
文献类型：
--
作者：
Park, Y;Lee, SW;Sung, YC
CpG DNA 已被认为是树突状细胞 (DC) 的强大刺激剂。在这项研究中，我们证明 CpG DNA 抑制 DC 的自发凋亡。 CpG DNA 上调细胞凋亡蛋白抑制剂 (cIAP) 以及 Bcl-2 和 Bcl-x(L)，但下调活性 caspase-3。尽管CpG DNA 激活p38 丝裂原激活蛋白激酶、细胞外信号相关激酶和磷脂酰肌醇-3'-OH 激酶(PI3K)，但只有阻断PI3K 才能抑制CpG DNA 诱导的DC 存活。此外，虽然Bcl-2和Bel-x(L)的表达依赖于PI3K和p38丝裂原激活蛋白激酶，但CpG DNA对cIAP的上调和活性caspase-3的下调需要PI3K激活，这表明DC中CpG DNA的抗凋亡活性中cIAP的上调依赖于PI3K。这项研究表明，CpG DNA 向 DC 提供生存信号，这可能是细菌 DNA 刺激和维持先天免疫反应的机制之一。
CpG DNA has been recognized as a powerful stimulant of dendritic cells (DCs). In this study, we demonstrate that CpG DNA inhibits spontaneous apoptosis of DCs. CpG DNA up-regulated cellular inhibitor of apoptosis proteins (cIAPs) as well as Bcl-2 and Bcl-x(L), but down-regulated active caspase-3. Although CpG DNA activated p38 mitogen-activated protein kinase, extracellular signal-related kinase, and phosphatidylinositide-3'-OH kinase (PI3K), only the blocking of PI3K inhibited the CpG DNA-induced DC survival. Moreover, while the expression of Bcl-2 and Bel-x(L) depends on both PI3K and p38 mitogen-activated protein kinase, the up-regulation of cIAPs and the down-regulation of active caspase-3 by CpG DNA require PI3K activation, suggesting PI3K-dependent upregulation of cIAPs in the antiapoptotic activity of CpG DNA in DCs. This study indicates that CpG DNA provides a survival signal to DCs, which might be one of mechanisms by which bacterial DNA stimulates and maintains the innate immune responses.