Histone Deacetylase 3 is an Epigenomic Brake in Macrophage Alternative Activation (microarray)

Macrophages, a key cellular component of inflammation, become functionally polarized in a signal- and context-specific manner. Th2 cytokines such as IL-4 polarize macrophages to a state of alternative activation that limits inflammation and promotes wound healing. Alternative activation is mediated by a transcriptional program that is influenced by epigenomic modifications including histone acetylation. To determine if Histone Deacetylase 3 (HDAC3) has a role in macrophage polarization including alternative activation, we have performed global gene expression analysis in macrophages with and without HDAC3 and with or without IL-4 exposure. From this data, we conclude that macrophages lacking histone deacetylase 3 (HDAC3) display a polarization phenotype similar to IL-4 induced alternative activation and furthermore are hyper-responsive to IL-4 stimulation. Mouse bone marrow derived macrophages were obtained from both control and HDAC3 KO animals and treated with vehicle control (BSA) or IL-4 for 24 hours. RNA was isolated and subjected to analysis using an Agilent Whole Genome Microarray Kit.