Low-Intensity Ultrasound Enhances Histone Acetylation and Inhibition of Interleukin 6 Messenger RNA Expression by the Histone Deacetylase Inhibitor Sodium Butyrate in Fibroblasts

J Ultrasound Med. 2017 May;36(5):879-885. doi: 10.7863/ultra.16.04020. Epub 2017 Feb 3.

Abstract

Objectives: Sodium butyrate, an inhibitor of histone deacetylase, has several therapeutic actions, including anti-inflammation. These actions depend on the concentration of sodium butyrate. In addition, lower concentrations have shown no effect on inflammation. Sonoporation by ultrasound can modify the permeability of the cell plasma membrane. Thus, the effects of sodium butyrate may be enhanced by the ultrasonic acoustics. Therefore, the facilitative effects of low-intensity ultrasound on histone acetylation and interleukin 6 (IL-6) regulation by sodium butyrate were investigated in this study.

Methods: Human dermal fibroblasts were treated with 1-mM sodium butyrate for 3 hours with 20 minutes of 0.1-W/cm2 pulsed or continuous ultrasound irradiation at the beginning of the sodium butyrate treatments.

Results: The combination of treatments with sodium butyrate and ultrasound significantly increased histone acetylation in fibroblasts (P < .05), whereas sodium butyrate could not increase histone acetylation. In addition, this combined treatment significantly suppressed the IL-6 messenger RNA expression level with lipopolysaccharide stimulation for 1 hour (P < .05). Meanwhile, the treatment with sodium butyrate alone could not suppress IL-6 messenger RNA expression in fibroblasts. These effects were achieved with both 20% pulsed and continuous ultrasound but not observed with ultrasound treatment alone.

Conclusions: These results suggest that low-intensity ultrasound treatment promotes the physiologic actions of sodium butyrate as a histone deacetylase inhibitor.

Keywords: butyrate; histone acetylation; interleukin 6; low-intensity ultrasound.

MeSH terms

  • Acetylation
  • Blotting, Western
  • Butyric Acid / pharmacology*
  • Cell Culture Techniques
  • Fibroblasts / metabolism*
  • Histone Deacetylase Inhibitors / pharmacology
  • Histones / metabolism*
  • Humans
  • Interleukin-6 / metabolism*
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Ultrasonic Waves*

Substances

  • Histone Deacetylase Inhibitors
  • Histones
  • Interleukin-6
  • RNA, Messenger
  • Butyric Acid