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

Biological & Pharmaceutical Bulletin
Yukihiko AramakiSeishi Tsuchiya

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.

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Citations

Dec 14, 2005·Bioorganic & Medicinal Chemistry Letters·Takahisa AnadaKazuo Sakurai
Dec 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Melissa K MiddletonEllen Puré

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