Histone hyperacetylation plays a role in augmentation of IL-4-induced IgE production in LPS-stimulated murine B-lymphocytes by sodium butyrate.
We previously reported the augmentation by sodium butyrate (NaBu) of IL-4-induced IgE production in LPS-stimulated murine B-lymphocytes. Histone deacetylase inhibition may be involved in the molecular mode of action of NaBu. Thus, this study was accomplished to examine the involvement of histone hyperacetylation in IL-4-induced class switching promotion by NaBu with a specific histone deacetylase inhibitor, trichostatin A (TSA). TSA was found to enhance IL-4-dependent IgE production in a concentration-dependent manner (0.3-30 nM) as did NaBu, although neither compound affected the IgE production in the absence of IL-4. The effect of combined addition of suboptimal concentrations of NaBu and TSA to the culture appeared to be additive, not synergistic. Moreover, the intense of enhancement of IgE production observed by addition of both compounds at optimal concentrations appeared to be equivalent to that obtained with each maximal concentration. Furthermore, enhancement of IgE production by TSA or NaBu was confirmed to be absolutely IL-4 dependent and was not due to the shift of kinetics. On the other hand, various cell cycle inhibitors such as caffeine and theophylline (G1 or G2-arrest), hydroxyurea (S-arrest), and colchicine (M-arrest), none of which have the ability to inhibit histone deacetylase, were shown to have no effect. These findings suggest that histone hyperacetylation plays an important regulatory role in the modification of IL-4-dependent class switching to C epsilon in LPS-stimulated murine B-cells by NaBu.
Yamamoto
I
I
Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University.
Matsunaga
T
T
Sakata
K
K
Nakamura
Y
Y
Doi
S
S
Hanmyou
F
F
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000096:biosynthesis*; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides; D051379:Mice
D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D008070:Lipopolysaccharides; D020148:Butyric Acid; D015847:Interleukin-4; D007073:Immunoglobulin E; C012589:trichostatin A