Cytokine induction by a bacterial DNA-specific modified base.
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.
Tsuchiya
Hiroyuki
H
Laboratory for Molecular Design of Pharmaceutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Matsuda
Tadashi
T
Harashima
Hideyoshi
H
Kamiya
Hiroyuki
H
D000225:Adenine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000818:Animals; D018899:CpG Islands / Q000235:genetics; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D004269:DNA, Bacterial / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*
D000225:Adenine; D016207:Cytokines; D004269:DNA, Bacterial; D009838:Oligodeoxyribonucleotides; C000730567:6-methyladenine