Inhibition of murine macrophage IL-12 production by natural and synthetic DNA.
DNA is a complex macromolecule whose immunological properties vary with sequence and structure. To determine whether DNA can inhibit immune responses, the effects of mammalian DNA and synthetic phosphodiester (Po) and phosphorothioate (Ps) oligonucleotides (ODNs) on IL-12 production were tested using murine macrophages. With bacterial DNA as a stimulant, calf thymus DNA and human placenta DNA blocked IL-12 production by splenic and bone marrow macrophages. A (dG)(30) Po ODN and all single-base Ps 30 mer ODNs were also effective inhibitors. The Ps ODNs also blocked IL-12 production induced by lipopolysaccharide (LPS) and a stimulatory Ps ODN. With the J774 cell line, single-base Ps ODNs inhibited IL-12 production induced by bacterial DNA, LPS, and a stimulatory Ps ODN. Together, these results indicate that DNA has inhibitory properties, suggesting that mammalian DNA could limit immune activation during inflammation and counteract the effects of bacterial DNA.
Pisetsky
D S
DS
Durham VA Medical Center, Durham, North Carolina, 27705, USA. dpiest@acpub.duke.edu
Reich
C F
CF
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D018899:CpG Islands; D004247:DNA / Q000276:immunology / Q000494:pharmacology*; D004274:DNA, Recombinant / Q000494:pharmacology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000235:genetics
D000276:Adjuvants, Immunologic; D004274:DNA, Recombinant; D009841:Oligonucleotides; D018664:Interleukin-12; D004247:DNA