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- W4387501696 abstract "Metabolic reprogramming is essential for the activation and functions of macrophages, including bacterial killing and cytokine production. Bromodomain-containing protein 4 (BRD4) has emerged as a critical regulator of innate immune response. However, the potential role of BRD4 in metabolic reprogramming of macrophage activation upon H. pylori infection remains unclear.Bone marrow-derived macrophages (BMDMs) from WT and Brd4-myeloid deletion conditional knockout mice (Brd4-CKO) were infected with H. pylori. RNA sequencing was performed to evaluate the differential gene expression between WT and Brd4-deficient BMDMs upon infection. An in vivo model of WT and Brd4-CKO mice was used to confirm the role of BRD4 in innate immune response to H. pylori infection.Depletion of Brd4 in BMDMs impaired H. pylori-induced glycolysis. Additionally, H. pylori-induced expression of glycolytic genes, including Glucose transporter type 1 (Glut1) and Hexokinase 2 (Hk2), was decreased in Brd4-deficient BMDMs. BRD4 was recruited to promoters of Glut1 and Hk2 via Hypoxia-inducible factor 1 alpha (HIF-1α), facilitating their expression. BRD4-mediated glycolysis stabilized H. pylori-induced nitric oxide synthase (Nos2) mRNA to produce nitric oxide (NO). The NO-mediated killing of H. pylori decreased in Brd4-deficient BMDMs, which was rescued by pyruvate. Furthermore, Brd4-CKO mice infected with H. pylori exhibited reduced gastric inflammation, increased H. pylori colonization and reduced iNOS expression in gastric macrophages.Our study identified BRD4 as a key regulator of HIF-1α-dependent glycolysis and macrophage activation. Furthermore, we demonstrate a novel regulatory role of BRD4 in innate immunity through glycolysis to stabilize Nos2 mRNA for NO production to eliminate H. pylori infection." @default.
- W4387501696 created "2023-10-11" @default.
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- W4387501696 date "2023-10-01" @default.
- W4387501696 modified "2023-10-13" @default.
- W4387501696 title "BRD4 regulates glycolysis-dependent Nos2 expression in macrophages upon H. pylori infection" @default.
- W4387501696 doi "https://doi.org/10.1016/j.jcmgh.2023.10.001" @default.
- W4387501696 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37820788" @default.
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