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Involvement of DNA-PKcs in the IL-6 and IL-12 response to CpG-ODN is mediated by its interaction with TRAF6 in dendritic cells.


ABSTRACT: CpG-ODN stimulates dendritic cells (DCs) to produce cytokines, which are important for pathogenesis of autoimmune disorders and vaccine strategy for cancer. CpG-ODN activates the TLR9/MyD88/TRAF6 cascade leading to activation of IKK-NF-?B and JNK, which are critical for production of pro-inflammatory cytokines. However, whether other molecules are involved in activation of CpG-ODN signaling is still not clear. Here we report that the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is involved in this activation process. DNA-PKcs-deficient DCs exhibited a defect in the IL-6 and IL-12 response to CpG-ODN in a dose- and time-dependent manner. Loss of DNA-PKcs impaired phosphorylation of IKK, I?B?, NF-?B and JNK in response to CpG-ODN. Interestingly, CpG-ODN was able to bind DNA-PKcs and induce its association and co-localization with TRAF6 in the absence of TLR9. Our data suggest that DNA-PKcs is a player in CpG-ODN signaling and may explain why DNA-PKcs is implicated in the pathogenic process of autoimmune disease.

SUBMITTER: Ma C 

PROVIDER: S-EPMC3606245 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Involvement of DNA-PKcs in the IL-6 and IL-12 response to CpG-ODN is mediated by its interaction with TRAF6 in dendritic cells.

Ma Chi C   Muranyi Marianna M   Chu Catherine H CH   Zhang Jianhua J   Chu Wen-Ming WM  

PloS one 20130322 3


CpG-ODN stimulates dendritic cells (DCs) to produce cytokines, which are important for pathogenesis of autoimmune disorders and vaccine strategy for cancer. CpG-ODN activates the TLR9/MyD88/TRAF6 cascade leading to activation of IKK-NF-κB and JNK, which are critical for production of pro-inflammatory cytokines. However, whether other molecules are involved in activation of CpG-ODN signaling is still not clear. Here we report that the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) i  ...[more]

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