Identification of the histone lysine demethylase KDM4A/JMJD2A as a novel epigenetic target in M1 macrophage polarization induced by oxidized LDL.

ABSTRACT: Oxidized low density lipoprotein (oxLDL) induces macrophage activation, an event essential for atherosclerosis. Emerging evidence supports that epigenetic regulation plays important roles in macrophage activation and function. However, it remains unclear which epigenetic modulator is responsible for oxLDL-induced macrophage activation. Here, we identify for the first time KDM4A (JMJD2A) as an epigenetic modifying enzyme that controls oxLDL-induced pro-inflammatory M1 polarization of macrophages. OxLDL triggered M1 polarization of murine and human macrophages, characterized by expression of iNOS and robust production of inflammatory cytokines (e.g., TNF-α, MCP-1, IL-1β). In contrast, protein level of the M2 marker Arg1 was clearly decreased after treated with oxLDL. Notably, exposure to oxL

SUBMITTER: Wang X 

PROVIDER: S-EPMC5777704 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature