Histone hyperacetylation mediates enhanced IL-1? production in LPS/IFN-?-stimulated macrophages.

ABSTRACT: Under the condition of lipopolysaccharide (LPS)/interferon (IFN)-? activation, macrophage metabolism is converted from oxidative phosphorylation to glycolysis. In the present work, we analysed whether glycolysis could affect interleukin (IL)-1? 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-?. Real-time polymerase chain reaction and enzyme-linked immunosorbent assay were used to determine IL-1? 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-1? production in LPS/IFN-?-activated macrophages. Moreover, increased production of IL-1? 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-1? in the absence of glycolytic metabolism. In conclusion, this study demonstrates that glycolytic metabolism could regulate IL-1? expression by increasing histone acetylation levels in LPS/IFN-?-stimulated macrophages.

SUBMITTER: Dong Z 

PROVIDER: S-EPMC7218666 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature