ArticleMolecular biology of the cell2014
Glycolysis-dependent histone deacetylase 4 degradation regulates inflammatory cytokine production.
Article in Molecular biology of the cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Mitochondrial dysfunction in sepsis-associated acute kidney injury: mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- Inflammation and aging-related disease: A transdisciplinary inflammaging framework.GeroScience · 2025Review
- Genetic Commonalities Between Metabolic Syndrome and Rheumatic Diseases Through Disease Interactome Modules.Journal of cellular and molecular medicine · 2025Article
- Histone deacetylases: the critical enzymes for microglial activation involved in neuropathic pain.Frontiers in pharmacology · 2025Review
- PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I IFN pathway.The Journal of experimental medicine · 2024Article
- Roles of Histone Deacetylase 4 in the Inflammatory and Metabolic Processes.Diabetes & metabolism journal · 2024Review
- Stress and Microglia: A Double-edged Relationship.Advances in neurobiology · 2024Review
- Interleukin 1β triggers synaptic and memory deficits in Herpes simplex virus type-1-infected mice by downregulating the expression of synaptic plasticity-related genes via the epigenetic MeCP2/HDAC4 complex.Cellular and molecular life sciences : CMLS · 2023Article
- Lyn-mediated glycolysis enhancement of microglia contributes to neuropathic pain through facilitating IRF5 nuclear translocation in spinal dorsal horn.Journal of cellular and molecular medicine · 2023Article
- HDAC4 in cancer: A multitasking platform to drive not only epigenetic modifications.Frontiers in molecular biosciences · 2023Review
- Epigenomic and transcriptomic analyses reveal differences between low-grade inflammation and severe exhaustion in LPS-challenged murine monocytes.Communications biology · 2022Article
- Role of Epigenetics in the Regulation of Immune Functions of the Skin.The Journal of investigative dermatology · 2021Review
- Epigenetic Modifiers: Anti-Neoplastic Drugs With Immunomodulating Potential.Frontiers in immunology · 2021Review
- Glycogen Synthase Kinase 3β Modulates the Inflammatory Response Activated by Bacteria, Viruses, and Parasites.Frontiers in immunology · 2021Review
- Epigenetic Regulation in Sepsis, Role in Pathophysiology and Therapeutic Perspective.Frontiers in medicine · 2021Review
- miR-29b attenuates histone deacetylase-4 mediated podocyte dysfunction and renal fibrosis in diabetic nephropathy.Journal of diabetes and metabolic disorders · 2020Article
- Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages.Cancers · 2020Review
- Functional Inhibition of Host Histone Deacetylases (HDACs) EnhancesFrontiers in immunology · 2020Article
- Particles from the Echinococcus granulosus Laminated Layer Inhibit CD40 Upregulation in Dendritic Cells by Interfering with Akt Activation.Infection and immunity · 2019Article
- Ammonia exposure induced abnormal expression of cytokines and heat shock proteins via glucose metabolism disorders in chicken neutrophils.Environmental science and pollution research international · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Activation of the inflammatory response is accompanied by a metabolic shift to aerobic glycolysis. Here we identify histone deacetylase 4 (HDAC4) as a new component of the immunometabolic program. We show that HDAC4 is required for efficient inflammatory cytokine production activated by lipopolysaccharide (LPS). Surprisingly, prolonged LPS treatment leads to HDAC4 degradation. LPS-induced HDAC4 degradation requires active glycolysis controlled by GSK3β and inducible nitric oxide synthase (iNOS). Inhibition of GSK3β or iNOS suppresses nitric oxide (NO) production, glycolysis, and HDAC4 degradation. We present evidence that sustained glycolysis induced by LPS treatment activates caspase-3, which cleaves HDAC4 and triggers its degradation. Of importance, a caspase-3-resistant mutant HDAC4 escapes LPS-induced degradation and prolongs inflammatory cytokine production. Our findings identify the GSK3β-iNOS-NO axis as a critical signaling cascade that couples inflammation to metabolic reprogramming and a glycolysis-driven negative feedback mechanism that limits inflammatory response by triggering HDAC4 degradation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.