Collaborative Action of NF-κB and p38 MAPK Is Involved in CpG DNA-Induced IFN-α and Chemokine Production in Human Plasmacytoid Dendritic Cells
| Autor: | Youko Osawa, Hisakazu Takatsuka, Saburo Yamamoto, Shigeharu Fujieda, Sumiko Iho, Takayuki Takahashi, Satomi Horiguchi, Yoshimasa Urasaki, Takasumi Matsuki, Rumiko Takauji |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Chemokine
Interferon Regulatory Factor-7 p38 mitogen-activated protein kinases Blotting Western Immunology Gene Expression CCL3 Enzyme-Linked Immunosorbent Assay p38 Mitogen-Activated Protein Kinases Humans Immunology and Allergy CXCL10 Gene biology Reverse Transcriptase Polymerase Chain Reaction NF-kappa B Interferon-alpha TLR9 hemic and immune systems Dendritic Cells Flow Cytometry Cell biology CpG site Toll-Like Receptor 9 Cancer research biology.protein CpG Islands Chemokines Signal transduction Signal Transduction |
| Zdroj: | The Journal of Immunology. 177:4841-4852 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.177.7.4841 |
| Popis: | CpG DNA induces plasmacytoid dendritic cells (pDC) to produce type I IFN and chemokines. However, it has not been fully elucidated how the TLR9 signaling pathway is linked to these gene expressions. We examined the mechanisms involving the TLR9 and type I IFN signaling pathways, in relation to CpG DNA-induced IFN-α, IFN regulatory factor (IRF)-7, and chemokines CXCL10 and CCL3 in human pDC. In pDC, NF-κB subunits p65 and p50 were constitutively activated. pDC also constitutively expressed IRF-7 and CCL3, and the gene expressions seemed to be regulated by NF-κB. CpG DNA enhanced the NF-κB p65/p50 activity, which collaborated with p38 MAPK to up-regulate the expressions of IRF-7, CXCL10, and CCL3 in a manner independent of type I IFN signaling. We then examined the pathway through which IFN-α is expressed. Type I IFN induced the expression of IRF-7, but not of IFN-α, in a NF-κB-independent way. CpG DNA enabled the type I IFN-treated pDC to express IFN-α in the presence of NF-κB/p38 MAPK inhibitor, and chloroquine abrogated this effect. With CpG DNA, IRF-7, both constitutively and newly expressed, moved to the nuclei independently of NF-κB/p38 MAPK. These findings suggest that, in CpG DNA-stimulated human pDC, the induction of IRF-7, CXCL10, and CCL3 is mediated by the NF-κB/p38 MAPK pathway, and that IRF-7 is activated upstream of the activation of NF-κB/p38 MAPK in chloroquine-sensitive regulatory machinery, thereby leading to the expression of IFN-α. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|