Novel Detection of Post-translational Modifications in Human Monocyte-derived Dendritic Cells After Chronic Alcohol Exposure: Role of Inflammation Regulator H4K12ac

Overview

Journal Sci Rep

Specialty Science

Date 2017 Sep 13

PMID 28894190

Citations 8

Authors

Tiyash Parira

Gloria Figueroa

Alejandra Laverde

Gianna Casteleiro

Mario E Gomez Hernandez

Francisco Fernandez-Lima

Marisela Agudelo

Affiliations

Soon will be listed here.

Abstract

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.

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