Cytokine induction by a bacterial DNA-specific modified base |
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Authors: | Tsuchiya Hiroyuki Matsuda Tadashi Harashima Hideyoshi Kamiya Hiroyuki |
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Institution: | Laboratory for Molecular Design of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. |
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Abstract: | Unmethylated CpG dinucleotides in DNA contribute to a rapid inflammatory response in mammals. Here we show that N(6)-methyladenine (N(6)-MeA), a bacterium-specific modified base, also causes cytokine production. An oligodeoxyribonucleotide (ODN) containing N(6)-MeA induced cytokines when injected into mice. Co-injection of N(6)-MeA and CpG ODNs enhanced cytokines 2- to 3-fold, as compared with the injection of a CpG ODN alone. Plasmid DNA containing N(6)-MeA, complexed with cationic lipids, induced IL-12. These results indicate that the bacterium-specific base, in addition to the unmethylated CpG motif, triggers the mammalian immune response, and suggest that N(6)-MeA-containing DNA could be useful for cellular immunotherapy and DNA vaccine. |
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Keywords: | N6-Methyladenine CpG Dam Acute inflammatory response Inflammatory cytokines |
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