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

• Published in: Biological & pharmaceutical bulletin Vol. 25; no. 3; pp. 351 - 355
• Main Authors: Aramaki, Yukihiko, Yotsumoto, Satoshi, Watanabe, Hiroyuki, Tsuchiya, Seishi
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01-03-2002; Maruzen; Japan Science and Technology Agency
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Base Sequence; Biological and medical sciences; CpG; DNA Primers; Fundamental and applied biological sciences. Psychology; Fundamental immunology; IL-12; Immunobiology; Interleukin-12 - biosynthesis; Lymphokines, interleukins ( function, expression); macrophage; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - metabolism; NADPH Oxidases - metabolism; NADPH–oxidase; NF-kappa B - metabolism; Organophosphorus Compounds - pharmacology; Reactive Oxygen Species; Regulatory factors and their cellular receptors; ROS; Thionucleotides - pharmacology; Enzyme; Cytokine; Rodentia; NADPH dehydrogenase; Biological activity; Immunomodulator; Vertebrata; Mammalia; Interleukin 2; Mouse; Animal; Adjuvant; Oligonucleotide; Oxidoreductases; Transcription factor NFκB; Mechanism of action; Humoral immunity; Macrophage
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.25.351

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 μM. 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)-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.