NADPH-Oxidase may Contribute to IL-12 Production in Macrophages Stimulated with CpG Phosphorothioate Oligodeoxynucleotides

概要

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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 1μM. A reactive oxygen species (ROS) scavenger, Nacetylcysteine, 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)-κB is one of the transcriptional factors involved in IL-12 gene expression, and indeed CpG-ODN activated NF-κB. 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-κB does not act as a predominant transcription factor for IL-12 secretion.
公益社団法人日本薬学会の論文
2002-03-01