Dataset Information

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

ACCESS DATA

Publications

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

Dong Zhen Z Li Ruoshui R Xu Lei L Xin Kaiyue K Xu Yamei Y Shi Haiming H Sun Aijun A Ge Junbo J

Immunology 20200407 2

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 ...[more]

PMID: 32061096

Similar Datasets

Project description:ObjectiveC/EBPβ, a crucial transcription factor, regulates innate immunity and inflammatory responses. However, the role played by C/EBPβ in alveolar macrophage (AM) inflammatory responses remains unknown. This study aimed to investigate the role and mechanism of C/EBPβ in alveolar macrophages (AMs) from the transcriptional level and to search for natural compounds targeting C/EBPβ.MethodsRat AMs were infected with Lv-sh-C/EBPβ and treated with LPS, and the expression levels of iNOS, TNF-α, IL-6, and IL-1β were measured by RT-qPCR, Western blotting, and ELISA. Mechanistically, transcriptome sequencing (RNA-seq) revealed changes in gene expression patterns in AMs after LPS stimulation and C/EBPβ knockdown. Functional enrichment analyses and rescue experiments identified and validated inflammation-associated cell signaling pathways regulated by C/EBPβ. Furthermore, virtual screening was used to search for natural compounds that inhibit C/EBPβ with the structure of helenalin as a reference.ResultsFollowing stimulation with LPS, AMs exhibited an increased expression of C/EBPβ. C/EBPβ knockdown significantly decreased the expression levels of inflammatory mediators. A total of 374 differentially expressed genes (DEGs) were identified between LPS-stimulated C/EBPβ knockdown and negative control cells. The NOD-like receptor signaling may be a key target for C/EBPβ, according to functional enrichment analyses of the DEGs. Further experiments showed that the muramyl dipeptide (MDP, NOD2 agonist) reversed the downregulation of inflammatory mediators and the NF-κB pathway caused by the C/EBPβ knockdown. The virtual screening revealed that N-caffeoyltryptophan, orilotimod, and petasiphenone have comparable pharmacological properties to helenalin (a known C/EBPβ inhibitor) and demonstrate a great binding capacity to C/EBPβ.ConclusionAblation of C/EBPβ may attenuate LPS-induced inflammatory damage in AMs by inhibiting the NOD2 receptor signaling pathway. Three natural compounds, N-caffeoyltryptophan, orilotimod, and petasiphenone, may be potential C/EBPβ inhibitors.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets