ArticleSurgery2014
Selective histone deacetylase-6 inhibition attenuates stress responses and prevents immune organ atrophy in a lethal septic model.
Article in Surgery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Advances in the Study of Immunosuppressive Mechanisms in Sepsis.Journal of inflammation research · 2023Review
- Role of HDAC6 inhibition in sepsis-induced acute respiratory distress syndrome (Review).Experimental and therapeutic medicine · 2021Review
- Histone Deacetylase Inhibitors: A Novel Strategy in Trauma and Sepsis.Shock (Augusta, Ga.) · 2019Review
- Histone Deacetylation Inhibitors as Therapy Concept in Sepsis.International journal of molecular sciences · 2019Review
- Protective effect of Cl-amidine against CLP-induced lethal septic shock in mice.Scientific reports · 2016Article
- Inhibition of histone deacetylase 6 restores intestinal tight junction in hemorrhagic shock.The journal of trauma and acute care surgery · 2016Article
- HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions.Oncotarget · 2016Article
- Assessment of plasma B7-H3 levels in pediatric patients with different degrees of surgical stress.BMC pediatrics · 2016Article
- Histone Deacetylase 6 Regulates Bladder Architecture and Host Susceptibility to Uropathogenic Escherichia coli.Pathogens (Basel, Switzerland) · 2016Article
- Inhibition of histone deacetylase 6 restores innate immune cells in the bone marrow in a lethal septic model.The journal of trauma and acute care surgery · 2016Article
- Selective inhibition of histone deacetylase 6 promotes survival in a rat model of hemorrhagic shock.The journal of trauma and acute care surgery · 2015Article
- Creating a "Prosurvival Phenotype" Through Histone Deacetylase Inhibition: Past, Present, and Future.Shock (Augusta, Ga.) · 2015Review
- Selective histone deacetylase 6 inhibition prolongs survival in a lethal two-hit model.The Journal of surgical research · 2015Article
- Hypothermia and valproic acid activate prosurvival pathways after hemorrhage.The Journal of surgical research · 2015Article
- Selective Inhibition of SIRT2 Improves Outcomes in a Lethal Septic Model.Current molecular medicine · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAn overproduction of corticosterone during severe sepsis results in increased apoptosis of immune cells, which may result in relative immunosuppression and an impaired ability to fight infections. We have previously demonstrated that administration of tubastatin A, a selective inhibitor of histone deacetylase-6 (HDAC6), improves survival in a lethal model of cecal ligation and puncture (CLP) in mice. The purpose of this study was to characterize the effects of this treatment on sepsis-induced stress responses and immune function.
methodsC57BL/6J mice were subjected to CLP, and 1 hour later given an intraperitoneal injection of either tubastatin A dissolved in dimethyl sulfoxide (DMSO), or DMSO only. Blood samples were collected to measure the levels of circulating corticosterone and adrenocorticotropic hormone (ACTH). Thymus and long bones (femur and tibia) were subjected to hematoxylin and eosin staining, and immunohistochemistry was utilized to detect cleaved-caspase 3 in the splenic follicles as a measure of cellular apoptosis.
resultsAll vehicle-treated CLP animals died within 3 days, and displayed increased corticosterone and decreased ACTH levels compared with the sham-operated group. These animals also developed atrophy of thymic cortex with a marked depletion of thymocytes. Tubastatin A treatment significantly attenuated the stress hormone abnormalities. Treated animals also had significantly lower percentages of thymic atrophy (95.0 ± 5.0 vs 42.5 ± 25.3; P = .0366), bone marrow depletion and atrophy (58.3 ± 6.5 vs 25.0 ± 14.4%; P = .0449), and cellular apoptosis in the splenic follicles (41.2 ± 3.7 vs 28.5 ± 4.3 per 40× field; P = .0354).
conclusionSelective inhibition of HDAC6 in this lethal septic model was associated with a significant blunting of the stress responses, with attenuated thymic and bone marrow atrophy, and decreased splenic apoptosis. Our findings identify a novel mechanism behind the survival advantage seen with tubastatin A treatment.
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Registered trials
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