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Chu, W. et al.

Chu, Gong, Li, Takabayashi, Ouyang, Chen, Lois, Chen, Li, Karin, Raz,

DNA-PKcs is required for activation of innate immunity by immunostimulatory DNA.

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 IKKbeta(-/-) revealed that both DNA-PKcs and IKKbeta 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.[1]

References

DNA-PKcs is required for activation of innate immunity by immunostimulatory DNA. Chu, W., Gong, X., Li, Z., Takabayashi, K., Ouyang, H., Chen, Y., Lois, A., Chen, D.J., Li, G.C., Karin, M., Raz, E. Cell (2000) [Pubmed]

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