Under 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.
Keywords: HDAC inhibitor; IL-1β; glycolysis; histone hyperacetylation; macrophage.
© 2020 The Authors. Immunology published by John Wiley & Sons Ltd.