DNA-PKcs is required for activation of innate immunity by immunostimulatory DNA (Retracted Article)
DNA-PKcs is required for activation of innate immunity by immunostimulatory DNA (Retracted Article)
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DOI：
10.1016/s0092-8674(00)00194-x
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发表时间：
2000-12-08
期刊：
影响因子：
64.5
通讯作者：
Raz, E
中科院分区：
文献类型：
--
作者：
Chu, WM;Gong, X;Raz, E
细菌DNA和相关的合成免疫刺激寡核苷酸(ISS-ODN)可刺激天然免疫。然而，启动响应细菌DNA和ISS-ODN的信号转导的分子识别机制尚未确定。在这里，我们证明了细菌DNA和ISS-ODN给缺乏DNA-PK催化亚单位(DNA-PKcs)的小鼠，以及体外刺激这些小鼠的BMDM会导致IL-6和IL-12的缺陷诱导。对ikkβ(-/-)的BMDM进一步分析表明，DNA-PKcs和ikkβ对ISS-ODN或细菌DNA的正常细胞因子的产生是必不可少的。ISS-ODN和细菌DNA激活DNA-PK，DNA-PK进而激活IKK和NF-kappaB。这些结果揭示了DNA-PKcs在先天免疫反应中的新作用以及DNA修复和先天免疫之间的联系。
Bacterial DNA and related synthetic immunostimulatory oligodeoxyribonucleotides (ISS-ODN) stimulate innate immunity. However, the molecular recognition mechanism that initiates signaling in response to bacterial DNA and ISS-ODN has not been identified. Herein, we demonstrate that administration of bacterial DNA and ISS-ODN to mice lacking the catalytic subunit of DNA-PK (DNA-PKcs) and in vitro stimulation of BMDM from these mice result in defective induction of IL-6 and IL-12. Further analysis using BMDM of IKK beta (-/-) revealed that both DNA-PKcs and IKK beta are essential for normal cytokine production in response to ISS-ODN or bacterial DNA. ISS-ODN and bacterial DNA activate DNA-PK, which in turn contributes to activation of IKK and NF-kappaB. These results reveal a novel role of DNA-PKcs in innate immune responses and a link between DNA repair and innate immunity.