Histone Hyperacetylation Mediates Enhanced IL‐1β Production in LPS/IFN‐γ stimulated Macrophages

Under the condition of LPS/IFN-gamma activation, macrophage metabolism is conversed from oxidative phosphorylation to glycolysis. In the present work, we analyzed whether glycolysis could affect IL-1beta expression through altering histone acetylation level in mouse bone marrow-derived macrophages. Immunocytochemistry and Western blot analysis are used to characterize histone acetylation in macrophages stimulated by LPS/IFN-gamma. RT-PCR and ELISA were used to determine IL-1beta production. Macrophages' metabolism was monitored in real time by Seahorse test. Our results showed that glycolytic metabolism could enhance the histone acetylation and promote the IL-1beta production in LPS/IFN-gamma activated macrophage. Moreover, increased production of IL-1beta by glycolysis was mediated through enhanced H3K9 acetylation. Importantly, it is found that high-dose of HDAC inhibitor could also significantly increase the expression of IL-1beta in the absence of glycolytic metabolism. In conclusion, this study demonstrates that glycolytic metabolism could regulate IL-1beta expression by increasing histone acetylation levels in LPS/IFN-gamma stimulated macrophages.