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.
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-inflammator...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3606245?pdf=render |
| _version_ | 1818330729588719616 |
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| author | Chi Ma Marianna Muranyi Catherine H Chu Jianhua Zhang Wen-Ming Chu |
| author_facet | Chi Ma Marianna Muranyi Catherine H Chu Jianhua Zhang Wen-Ming Chu |
| author_sort | Chi Ma |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T13:08:35Z |
| format | Article |
| id | doaj.art-86c6fdb07d81493890d0055c18adc8fd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T13:08:35Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-86c6fdb07d81493890d0055c18adc8fd2022-12-21T23:44:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5807210.1371/journal.pone.0058072Involvement of DNA-PKcs in the IL-6 and IL-12 response to CpG-ODN is mediated by its interaction with TRAF6 in dendritic cells.Chi MaMarianna MuranyiCatherine H ChuJianhua ZhangWen-Ming ChuCpG-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.http://europepmc.org/articles/PMC3606245?pdf=render |
| spellingShingle | Chi Ma Marianna Muranyi Catherine H Chu Jianhua Zhang Wen-Ming Chu 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. PLoS ONE |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
| url | http://europepmc.org/articles/PMC3606245?pdf=render |
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