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TNF promotes SREBP activity to regulate macrophage polarization and tissue repair

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE129229 | GEO | 2019/04/03

REPOSITORIES: GEO

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TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [RNA-seq]

Project description:TNF-mediated macrophage polarization is important for inflammatory disease pathogenesis, but mechanisms that regulate polarization are not well understood. Transcriptomic and epigenomic analysis of the TNF response in primary human macrophages revealed late phase activation of SREBP2, the master regulator of cholesterol biosynthesis genes. TNF stimulation extended the genomic profile of SREBP2 occupancy to include binding to and activation of inflammatory and interferon response genes independently of its functions in sterol metabolism. Genetic ablation of SREBP function shifted the balance of macrophage polarization from M1 to an M2-like reparative phenotype in peritonitis and skin wound healing models. Genetic ablation of SREBP activity in myeloid cells or topical pharmacological inhibition of SREBP improved skin wound healing under homeostatic and chronic inflammatory conditions. Our results identify a new function and mechanism of action for SREBP2 in augmenting TNF-induced M1 macrophage polarization and inflammation, and open therapeutic avenues for promoting wound repair.

2019-04-03 | GSE129210 | GEO

TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [scRNA-seq]

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TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [ChIP-seq]

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TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [ATAC-seq]

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TNF promotes SREBP activity to regulate macrophage polarization and tissue repair

Project description:TNF promotes SREBP activity to regulate macrophage polarization and tissue repair

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TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [scRNA-seq]

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TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [RNA-seq]

Project description:TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [RNA-seq]

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TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [ATAC-seq]

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TNF promotes SREBP activity to regulate macrophage polarization and tissue repair [ChIP-seq]

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The Cytokine TNF Promotes Transcription Factor SREBP Activity and Binding to Inflammatory Genes to Activate Macrophages and Limit Tissue Repair.

Project description:Cytokine tumor necrosis factor (TNF)-mediated macrophage polarization is important for inflammatory disease pathogenesis, but the mechanisms regulating polarization are not clear. We performed transcriptomic and epigenomic analysis of the TNF response in primary human macrophages and revealed late-phase activation of SREBP2, the master regulator of cholesterol biosynthesis genes. TNF stimulation extended the genomic profile of SREBP2 occupancy to include binding to and activation of inflammatory and interferon response genes independently of its functions in sterol metabolism. Genetic ablation of SREBP function shifted the balance of macrophage polarization from an inflammatory to a reparative phenotype in peritonitis and skin wound healing models. Genetic ablation of SREBP activity in myeloid cells or topical pharmacological inhibition of SREBP improved skin wound healing under homeostatic and chronic inflammatory conditions. Our results identify a function and mechanism of action for SREBPs in augmenting TNF-induced macrophage activation and inflammation and open therapeutic avenues for promoting wound repair.

| S-EPMC6709581 | biostudies-literature

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