Histone hyperacetylation mediates enhanced IL‐1β production in LPS/IFN‐γ‐stimulated macrophages

• DOI: 10.1111/imm.13183
• Publication Date: 2020-02-15T11:39:06Z
• Authors: Zhen Dong; Ruoshui Li; Lei Xu; Kaiyue Xin; Yamei Xu; Haiming Shi; Aijun Sun; Junbo Ge
• Keywords: Lipopolysaccharides; 0301 basic medicine; Macrophages; Interleukin-1beta; Primary Cell Culture; Acetylation; Original Articles; Macrophage Activation; Recombinant Proteins; Histones; Interferon-gamma; Mice; 03 medical and health sciences; Animals; Glycolysis; Cells, Cultured

SummaryUnder the condition of lipopolysaccharide (LPS)/interferon (IFN)‐γ activation, macrophage metabolism is converted from oxidative phosphorylation to glycolysis. In the present work, we analysed whether glycolysis could affect interleukin (IL)‐1β expression through altering histone acetylation levels in mouse bone marrow‐derived macrophages. Immunocytochemistry and Western blot analysis are used to characterize histone acetylation in macrophages stimulated by LPS/IFN‐γ. Real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay were used to determine IL‐1β production. The metabolism of macrophages was monitored in real‐time by the Seahorse test. Our results showed that glycolytic metabolism could enhance histone acetylation and promote IL‐1β production in LPS/IFN‐γ‐activated macrophages. Moreover, increased production of IL‐1β by glycolysis was mediated through enhanced H3K9 acetylation. Importantly, it was found that a high dose of histone deacetylase inhibitor could also significantly increase the expression of IL‐1β in the absence of glycolytic metabolism. In conclusion, this study demonstrates that glycolytic metabolism could regulate IL‐1β expression by increasing histone acetylation levels in LPS/IFN‐γ‐stimulated macrophages.