NADPH-oxidase may contribute to IL-12 production in macrophages stimulated with CpG phosphorothioate oligodeoxynucleotides

Biol Pharm Bull. 2002 Mar;25(3):351-5. doi: 10.1248/bpb.25.351.

Abstract

CpG oligodeoxynucleotides (CpG-ODN) could be expectes to act as an adjuvant for humoral and cellular immunities. The aim of this study was to clarify the mechanism of macrophage activation induced by CpG-ODN. Macrophage activation by CpG-ODN was evaluated by measurement of IL-12 secretion. IL-12 secretion by Cp-ODN was dose-dependent and saturation was observed at 1 microM. A reactive oxygen species (ROS) scavenger, N-acetylcysteine, inhibited IL-12 secretion, suggesting that the intracellular redox state is important for the activation of macrophages by CpG-ODN. IL-12 secretion was also inhibited by NADPH-oxidase inhibitors, suggesting that ROS generated by NADPH-oxidase is involved in the immunostimulatory effect of CpG-ODN. Nuclear factor (NF)-kappaB is one of the transcriptional factors involved in IL-12 gene expression, and indeed CpG-ODN activated NF-kappaB. However, NADPH-oxidase inhibitors did not affect the activation. These results indicated that NADPH-oxidase plays a crucial role in macrophage activation by CpG-ODN and NF-kappaB does not act as a predominant transcription factor for IL-12 secretion.

MeSH terms

  • Base Sequence
  • DNA Primers
  • Interleukin-12 / biosynthesis*
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism
  • NADPH Oxidases / metabolism*
  • NF-kappa B / metabolism
  • Organophosphorus Compounds / pharmacology
  • Reactive Oxygen Species
  • Thionucleotides / pharmacology*

Substances

  • DNA Primers
  • NF-kappa B
  • Organophosphorus Compounds
  • Reactive Oxygen Species
  • Thionucleotides
  • Interleukin-12
  • NADPH Oxidases