ArticlePloS one2016
Sirtuin-2 Regulates Sepsis Inflammation in ob/ob Mice.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 56 citations in OpenAlex.
- Epigenetic programming of macrophages across inflammatory and malignant diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- SIRT2 mitigates radiation-induced oral mucositis by promoting homologous recombination-mediated DNA double-strand break repair in epithelial stem cells.Cancer letters · 2026Article
- SIRT2 Regulates EX VIVO PBMC Adhesion in Septic Shock Patients.Shock (Augusta, Ga.) · 2026Article
- Hyaluronan 35 prevents endotoxin-mediated dysregulated skeletal muscle proteostasis during ethanol exposure.American journal of physiology. Endocrinology and metabolism · 2026Article
- Molecular mechanisms and functions of protein acetylation in sepsis and sepsis-associated organ dysfunction.Cellular & molecular biology letters · 2025Review
- Mitoquinol improves phagocytosis and glycolysis in ethanol-exposed macrophages via HIF-1α-PFKP axis.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Macrophage metabolism in inflammatory heart disease: new insights and therapeutic implications.Frontiers in medicine · 2025Review
- Drugs Targeting Sirtuin 2 Exhibit Broad-Spectrum Anti-Infective Activity.Pharmaceuticals (Basel, Switzerland) · 2024Review
- SIRT2 as a potential new therapeutic target for Alzheimer's disease.Neural regeneration research · 2024Review
- MiR-15b-5p and PCSK9 inhibition reduces lipopolysaccharide-induced endothelial dysfunction by targeting SIRT4.Cellular & molecular biology letters · 2023Article
- SIRT2-PFKP interaction dysregulates phagocytosis in macrophages with acute ethanol-exposure.Frontiers in immunology · 2022Article
- Protein acetylation in cardiac aging.Journal of molecular and cellular cardiology · 2021Review
- Article
- Understanding the Potential Role of Sirtuin 2 on Aging: Consequences of SIRT2.3 Overexpression in Senescence.International journal of molecular sciences · 2021Article
- Emerging therapeutic targets for sepsis.Expert opinion on therapeutic targets · 2021Review
- Ethanol Exposure Attenuates Immune Response in Sepsis via Sirtuin 2 Expression.Alcoholism, clinical and experimental research · 2021Article
- Macrophages in Chronic Liver Failure: Diversity, Plasticity and Therapeutic Targeting.Frontiers in immunology · 2021Review
- Sirtuin 2 expression levels may predict the progression of sepsis survivors to chronic critical illness.Annals of translational medicine · 2021Article
- Staging and Personalized Intervention for Infection and Sepsis.Surgical infections · 2020Review
- BxPC-3-Derived Small Extracellular Vesicles Induce FOXP3+ Treg through ATM-AMPK-Sirtuins-Mediated FOXOs Nuclear Translocations.iScience · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectiveObesity increases morbidity and resource utilization in sepsis patients. Sepsis transitions from early/hyper-inflammatory to late/hypo-inflammatory phase. Majority of sepsis-mortality occurs during the late sepsis; no therapies exist to treat late sepsis. In lean mice, we have shown that sirtuins (SIRTs) modulate this transition. Here, we investigated the role of sirtuins, especially the adipose-tissue abundant SIRT-2 on transition from early to late sepsis in obese with sepsis.
methodsSepsis was induced using cecal ligation and puncture (CLP) in ob/ob mice. We measured microvascular inflammation in response to lipopolysaccharide/normal saline re-stimulation as a "second-hit" (marker of immune function) at different time points to track phases of sepsis in ob/ob mice. We determined SIRT-2 expression during different phases of sepsis. We studied the effect of SIRT-2 inhibition during the hypo-inflammatory phase on immune function and 7-day survival. We used a RAW264.7 (RAW) cell model of sepsis for mechanistic studies. We confirmed key findings in diet induced obese (DIO) mice with sepsis.
resultsWe observed that the ob/ob-septic mice showed an enhanced early inflammation and a persistent and prolonged hypo-inflammatory phase when compared to WT mice. Unlike WT mice that showed increased SIRT1 expression, we found that SIRT2 levels were increased in ob/ob mice during hypo-inflammation. SIRT-2 inhibition in ob/ob mice during the hypo-inflammatory phase of sepsis reversed the repressed microvascular inflammation in vivo via activation of endothelial cells and circulating leukocytes and significantly improved survival. We confirmed the key finding of the role of SIRT2 during hypo-inflammatory phase of sepsis in this project in DIO-sepsis mice. Mechanistically, in the sepsis cell model, SIRT-2 expression modulated inflammatory response by deacetylation of NFκBp65.
conclusionSIRT-2 regulates microvascular inflammation in obese mice with sepsis and may provide a novel treatment target for obesity with sepsis.
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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.