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DNA and its cationic lipid complexes induce CpG motif‐dependent activation of murine dendritic cells
Author(s) -
Yoshinaga Takaharu,
Yasuda Kei,
Ogawa Yoshiyuki,
Nishikawa Makiya,
Takakura Yoshinobu
Publication year - 2007
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02451.x
Subject(s) - naked dna , cpg site , cpg oligodeoxynucleotide , biology , cationic liposome , microbiology and biotechnology , dna , tlr9 , transfection , plasmid , dna methylation , gene , biochemistry , gene expression
Summary Unmethylated CpG motifs in bacterial DNA, but not in vertebrate DNA, are known to trigger an inflammatory response of antigen‐presenting cells (APC). In this study, we investigated the cytokine release from murine dendritic cells (DC) by the addition of various types of DNA in the free or complexed form with cationic lipids. Naked plasmid DNA and Escherichia coli DNA with immunostimulatory unmethylated CpG motifs induced pro‐inflammatory cytokine secretion from granulocyte–macrophage colony‐stimulating factor (GM‐CSF)‐cultured bone marrow‐derived DC and the DC cell‐line, DC2.4 cells, though vertebrate calf thymus DNA (CT DNA) with less CpG motifs did not. These characteristics differed from mouse peritoneal resident macrophages that do not respond to any naked DNA. The amount of cytokines released from the DC was significantly increased by complex formation with cationic lipids when CpG‐motif positive DNAs were used. Unlike murine macrophages or Flt‐3 L cultured DC, GM‐CSF DC did not release inflammatory cytokines in response to the addition of CT DNA/cationic lipid complex, suggesting that the activation is completely dependent on CpG motifs. Taken together, the results of the present study demonstrate that murine DC produce pro‐inflammatory cytokines upon stimulation with CpG‐containing DNAs and the responses are enhanced by cationic lipids. These results also suggest that DC are the major cells that respond to naked CpG DNA in vivo , although both DC and macrophages will release inflammatory cytokines after the administration of a DNA/cationic lipid complex.