Novel detection of post-translational modifications in human monocyte-derived dendritic cells after chronic alcohol exposure: Role of inflammation regulator H4K12ac

Sci Rep. 2017 Sep 11;7(1):11236. doi: 10.1038/s41598-017-11172-6.


Previous reports on epigenetic mechanisms involved in alcohol abuse have focus on hepatic and neuronal regions, leaving the immune system and specifically monocyte-derived dendritic cells (MDDCs) understudied. Our lab has previously shown histone deacetylases are modulated in cells derived from alcohol users and after in vitro acute alcohol treatment of human MDDCs. In the current study, we developed a novel screening tool using matrix assisted laser desorption ionization-fourier transform-ion cyclotron resonance mass spectrometry (MALDI-FT-ICR MS) and single cell imaging flow cytometry to detect post-translational modifications (PTMs) in human MDDCs due to chronic alcohol exposure. Our results demonstrate, for the first time, in vitro chronic alcohol exposure of MDDCs modulates H3 and H4 and induces a significant increase in acetylation at H4K12 (H4K12ac). Moreover, the Tip60/HAT inhibitor, NU9056, was able to block EtOH-induced H4K12ac, enhancing the effect of EtOH on IL-15, RANTES, TGF-β1, and TNF-α cytokines while restoring MCP-2 levels, suggesting that H4K12ac may be playing a major role during inflammation and may serve as an inflammation regulator or a cellular stress response mechanism under chronic alcohol conditions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholism / pathology*
  • Cells, Cultured
  • Dendritic Cells / chemistry*
  • Dendritic Cells / drug effects*
  • Flow Cytometry
  • Histones / metabolism
  • Humans
  • Protein Processing, Post-Translational*
  • Proteome / analysis*
  • Single-Cell Analysis
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Histones
  • Proteome