An Increase in Histone Acetylation and IL-2 Antagonizing the Immunoinhibitory Effect Are Necessary for Augmentation by Butyrate of in Vitro Anti-TNP Antibody Production
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概要
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We investigated the role of histone acetylation in the promotion of antigen-specific antibody production in murine B cells induced by sodium butyrate (NaBu) plus interleukin 2 (IL-2). NaBu dose dependently increased the acetylation levels of histone H4 at concentrations which effectively enhanced anti-trinitrophenyl (TNP) antibody production in the presence of IL-2. Among other short-chain fatty acids and NaBu analogs, propionate, valerate and vinylacetate were effective in the presence of IL-2 in increasing both antibody production and the histone H4 acetylation level, but acetate, α-, β- and γ-hydroxybutyrates and α-, β- and γ-aminobutyrates were not effective, even in the presence of IL-2. The effect of the specific histone deacetylase inhibitor trichostatin A (TSA), which enhances anti-TNP antibody production without IL-2,was markedly inhibited by adding NaBu simultaneously. However, the effect of TSA was neither inhibited nor potentiated by NaBu in the presence of IL-2. Splenic B cells treated with NaBu, TSA and both together in the presence or absence of IL-2 showed almost the same increased acetylation level of histone H4. These results suggest that the NaBu-induced enhancement of anti-TNP antibody production in the presence of IL-2 is mediated through a moderate increase in the level of histone acetylation and that NaBu has both stimulating and inhibiting activities for anti-TNP antibody production, the latter of which is overcome by IL-2.
- 公益社団法人日本薬学会の論文
- 1999-12-15
著者
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Okamura Takayuki
Department of Medicine And Clinical Science, Yamaguchi University Graduate School of Medicine
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YAMAMOTO Itaru
Department of Radiology, Kanazawa Medical University
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GOHDA Eiichi
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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Okamura Takayuki
Department Of Immunochemistry Faculty Of Pharmaceutical Sciences Okayama University
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Yamamoto Itaru
Department Of Immunochemistry Faculty Of Pharmaceutical Science Okayama University
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Gohda Eiichi
Department Of Immunochemistry Division Of Pharmaceutical Sciences Okayama University Graduate School
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KOHGE Takashi
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University
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Yamamoto Itaru
Dep. Of Immunochemistry Fac. Of Pharmaceutical Sciences Okayama Univ.
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Kohge Takashi
Department Of Immunochemistry Faculty Of Pharmaceutical Sciences Okayama University
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GOHDA Eiichi
Department of Biochemistry, Faculty of Dentistry, Osaka University
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