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.
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, alpha-, beta- and gamma-hydroxybutyrates and alpha-, beta- and gamma-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.
Okamura
T
T
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Gohda
E
E
Kohge
T
T
Yamamoto
I
I
D000107:Acetylation; D000818:Animals; D000917:Antibody Formation; D002087:Butyrates / Q000494:pharmacology*; D005260:Female; D006657:Histones / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014301:Trinitrobenzenes / Q000276:immunology*
D002087:Butyrates; D006657:Histones; D007376:Interleukin-2; D014301:Trinitrobenzenes