Involvement of DNA-PKcs in the IL-6 and IL-12 Response to CpG-ODN Is Mediated by Its Interaction with TRAF6 in Dendritic CellsReportar como inadecuado




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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 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, IκBα, NF-κB 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.



Autor: Chi Ma, Marianna Muranyi, Catherine H. Chu, Jianhua Zhang, Wen-Ming Chu

Fuente: http://plos.srce.hr/



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