ArticleThe journal of trauma and acute care surgery2015
Inhibition of histone deacetylase 6 improves long-term survival in a lethal septic model.
Article in The journal of trauma and acute care surgery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Systematic review and meta-analysis of experimental studies evaluating the organ protective effects of histone deacetylase inhibitors.Translational research : the journal of laboratory and clinical medicine · 2019Pooled it
- Lactylated Histone H3K18 as a Potential Biomarker for the Diagnosis and Predicting the Severity of Septic Shock.Frontiers in immunology · 2021Trial
- Therapeutic potential of HDAC6 inhibitor Tubastatin A in health and diseases: current perspective and future directions.Military Medical Research · 2026Review
- Molecular mechanisms and functions of protein acetylation in sepsis and sepsis-associated organ dysfunction.Cellular & molecular biology letters · 2025Review
- Gut microbiota-derived acetic acids promoted sepsis-induced acute respiratory distress syndrome by delaying neutrophil apoptosis through FABP4.Cellular and molecular life sciences : CMLS · 2024Article
- Autophagy: a necessary evil in cancer and inflammation.3 Biotech · 2024Review
- Unveiling the modulation ofFrontiers in microbiology · 2024Article
- Protective effect of HDACIs in improves survival and organ injury after CLP-induced sepsis.Surgery open science · 2023Article
- HDAC6 inhibition: a significant potential regulator and therapeutic option to translate into clinical practice in renal transplantation.Frontiers in immunology · 2023Review
- Modified Suberoylanilide Hydroxamic Acid Reduced Drug-Associated Immune Cell Death and Organ Damage under Lipopolysaccharide Inflammatory Challenge.ACS pharmacology & translational science · 2022Article
- Chasing a Breath of Fresh Air in Cystic Fibrosis (CF): Therapeutic Potential of Selective HDAC6 Inhibitors to Tackle Multiple Pathways in CF Pathophysiology.Journal of medicinal chemistry · 2022Review
- Role of HDAC6 inhibition in sepsis-induced acute respiratory distress syndrome (Review).Experimental and therapeutic medicine · 2021Review
- Selective Targeting of Epigenetic Readers and Histone Deacetylases in Autoimmune and Inflammatory Diseases: Recent Advances and Future Perspectives.Journal of personalized medicine · 2021Review
- A competing endogenous RNA network reveals key lncRNAs associated with sepsis.Molecular genetics & genomic medicine · 2021Article
- Preclinical and clinical progress for HDAC as a putative target for epigenetic remodeling and functionality of immune cells.International journal of biological sciences · 2021Review
- Class IIa HDAC inhibitor TMP195 alleviates lipopolysaccharide-induced acute kidney injury.American journal of physiology. Renal physiology · 2020Article
- Megakaryocytes contain extranuclear histones and may be a source of platelet-associated histones during sepsis.Scientific reports · 2020Article
- HDAC6-specific inhibitor suppresses Th17 cell function via the HIF-1α pathway in acute lung allograft rejection in mice.Theranostics · 2020Article
- Targeting Macrophages as a Therapeutic Option in Coronavirus Disease 2019.Frontiers in pharmacology · 2020Article
- Natural Products Impacting DNA Methyltransferases and Histone Deacetylases.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWe recently demonstrated that suberoylanilide hydroxamic acid, a broad-spectrum histone deacetylase (HDAC) inhibitor that inhibits HDACs 1, 2, 3, and 6, improves survival in a mouse model of cecal ligation and puncture (CLP)-induced lethal sepsis. The current study was undertaken to determine the effect of selective inhibition of HDAC isoform on survival, key cytokine production, organ injury, bacteria clearance, and cell apoptosis.
methodsIn Experiment 1, C57BL/6J mice were subjected to CLP and, 1 hour later, given intraperitoneal injections of (1) Tubastatin A (inhibitor of HDAC6) dissolved in dimethyl sulfoxide (DMSO), (2) MS-275 (inhibitor of HDACs 1, 2, and 3) in DMSO, and (3) DMSO only. Survival was monitored for 10 days. In Experiment 2, 1 hour after CLP, animals were treated with DMSO vehicle or Tubastatin A. Sham-operated animals served as control. Peritoneal fluid and blood samples were collected for measurement of cytokines at 24 hours or 48 hours. Blood at 48 hours was also used to determine bacteria load. Liver was harvested to evaluate acute liver injury. In Experiment 3, Primary splenocytes were used to assess cytokine responses and phagocytosis. Macrophages were cultured and harvested 3 hours and 6 hours after lipopolysaccharide stimulation in the absence or presence of Tubastatin A to analyze cell apoptosis.
resultsAnimals treated with Tubastatin A, but not MS-275, displayed a significant improvement in survival. Moreover, Tubastatin A significantly inhibited cytokine production in peritoneal fluid and plasma as well as in supernatant from splenocytes stimulated with lipopolysaccharide. Tubastatin A significantly attenuated acute liver injury, increased blood bacteria clearance and splenocyte phagocytosis, and decreased macrophage apoptosis.
conclusionHDAC6 inhibition significantly improves survival, reduces "cytokine storm," attenuates acute livery injury, increases bacteria clearance and immune cell phagocytosis, and inhibits macrophage apoptosis in a lethal mouse CLP model.
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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.