DNA-PKcs Is Required for Activation of Innate Immunity by Immunostimulatory DNA

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• 作者：Wen-Ming Chu ; Xing Gong ; Zhi-Wei Li ; Kenji Takabayashi ; Hong-Hai Ouyang ; Yi Chen ; Augusto Lois ; David J. Chen ; Gloria C. Li ; Michael Karin and Eyal Raz
• 刊名：Cell
• 出版年：2000
• 出版时间：8 December 2000
• 年：2000
• 卷：103
• 期：6
• 页码：909-918
• 全文大小：501 K

文摘

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 IKKβ^−/− revealed that both DNA-PKcs and IKKβ 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-κB. These results reveal a novel role of DNA-PKcs in innate immune responses and a link between DNA repair and innate immunity.