Anisomycin protects against sepsis by attenuating IκB kinase-dependent NF-κB activation and inflammatory gene expression

Park, Gyoung Lim; Park, Minkyung; Min, Jeong‐Ki; Park, Young-Jun; Chung, Sung Min; Lee, Seon-Jin

doi:10.5483/bmbrep.2021.54.11.063

Cited by 8 publications

(3 citation statements)

References 16 publications

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“…Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms, such as bacteria and viruses (13). The primary syndromes of sepsis are systemic inflammation, organ hypoperfusion, and even septic shock (14). With an increased understanding of the Surviving Sepsis Campaign guidelines for diagnosis and treatment, drugs and support methods for multiple organ function have been developed and have increased the short-term mortality rate of patients with sepsis to ~20% (15).…”

Section: Discussionmentioning

confidence: 99%

MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils

Miao

Huang

2023

Exp Ther Med

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Sepsis is an infection-induced systemic inflammatory response syndrome accompanied by multiple organ injury and failure. MCC950, an inhibitor of NLR family pyrin domain containing 3 (NLRP3), can alleviate the inflammatory response and relieve inflammation-induced injury. The aim of the present study was to explore the efficacy of MCC950 in lipopolysaccharide (LPS)-induced inflammation and elucidate the underlying mechanisms. Based on a prior study, C57BL/6 mice were divided into three groups: Control, LPS, and LPS + MCC950. The mice were administered 10 mg/kg LPS to induce sepsis and 10 mg/kg MCC950 to treat sepsis 6 h before and after LPS injection. Histopathological imaging revealed organ morphology and damage during inflammation, and MCC950 alleviated organ damage and dysfunction. MCC950 prevented LPS-induced inflammatory responses by reducing inflammatory cytokine levels in the blood. To explore the mechanism by which MCC950 functions, blood neutrophils were isolated and a series of tests were performed. As revealed by measuring reactive oxygen species levels and Annexin V/PI staining of neutrophils, MCC950 reduced oxidative stress and programmed death induced by LPS. Western blotting was used to assess the protein levels of pyroptosis-related markers, including GSDMD, NLRP3, and caspase-1, in neutrophils to further explore the form of death. MCC950 reduced LPS-induced pyroptosis in neutrophils. The results of the survival analysis revealed that MCC950 increased the survival rates of mice within 72 h of LPS injection. MCC950 may be an effective treatment for sepsis that targets neutrophil pyroptosis.

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Section: Discussionmentioning

confidence: 99%

MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils

Miao

Huang

2023

Exp Ther Med

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“…After the injection, mice were monitored for 12 days post-treatment, and blood, tissues, or relevant samples were collected for subsequent analyses. For Cecal ligation and puncture (CLP) induction of sepsis, CLP was surgically performed on mice according to the original protocol as developed by Lee et al [24], with some modifications. Briefly, the mice were anesthetized using an intraperitoneal injection of avertin (500 mg/kg).…”

Section: Animal Experimentationsmentioning

confidence: 99%

Anti-Inflammatory Effects of Idebenone Attenuate LPS-Induced Systemic Inflammatory Diseases by Suppressing NF-κB Activation

Choi,

Cho,

Park

et al. 2024

Antioxidants

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Inflammation is a natural protective process through which the immune system responds to injury, infection, or irritation. However, hyperinflammation or long-term inflammatory responses can cause various inflammatory diseases. Although idebenone was initially developed for the treatment of cognitive impairment and dementia, it is currently used to treat various diseases. However, its anti-inflammatory effects and regulatory functions in inflammatory diseases are yet to be elucidated. Therefore, this study aimed to investigate the anti-inflammatory effects of idebenone in cecal ligation puncture-induced sepsis and lipopolysaccharide-induced systemic inflammation. Murine models of cecal ligation puncture-induced sepsis and lipopolysaccharide-induced systemic inflammation were generated, followed by treatment with various concentrations of idebenone. Additionally, lipopolysaccharide-stimulated macrophages were treated with idebenone to elucidate its anti-inflammatory effects at the cellular level. Idebenone treatment significantly improved survival rate, protected against tissue damage, and decreased the expression of inflammatory enzymes and cytokines in mice models of sepsis and systemic inflammation. Additionally, idebenone treatment suppressed inflammatory responses in macrophages, inhibited the NF-κB signaling pathway, reduced reactive oxygen species and lipid peroxidation, and normalized the activities of antioxidant enzyme. Idebenone possesses potential therapeutic application as a novel anti-inflammatory agent in systemic inflammatory diseases and sepsis.

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“…As a result, effective treatments for inflammatory illnesses are developed by searching molecular targets that specifically target different inflammatory pathways. 2,3 The adaptive immune response, which includes T helper (Th) cell subpopulations, such as Th1 and Th17 cells, is a crucial defense mechanism to shield host from infection. By secreting Th1-type cytokines, such as interferon gamma (IFN-γ) and IL-2, Th1 cells supported cellmediated immune responses.…”

Section: Introductionmentioning

confidence: 99%

IL2RB affects Th1/Th2 and Th17 responses of peripheral blood mononuclear cells from septic patients

Zhou

Zhang

Zhuang

2023

Allergol Immunopathol

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Background: Immune dysfunction is a common and serious complication of sepsis. This study finds key genes linked to immunity in sepsis. Methods: The “Limma package” was used to analyze GSE154918 datasets for differentially expressed genes. The differentially expressed genes were then enriched for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and interleukin 2 receptor subunit Beta (IL2RB) protein coding gene was chosen for investigation. IL2RB expression in peripheral blood mononuclear cells (PBMC) was assessed by polymerase chain reaction. White blood cells of septic patients and healthy controls were collected from hospitals and linked with acute physiology and chronic health evaluation (APACHE) II, sequential organ failure assessment (SOFA), C-reactive protein (CRP), and procalcitonin (PCT) of septic patients using Pearson’s correlation analysis. PBMC cells were transfected with IL2RB, and the effect of transfection was observed on cellular interferon gamma (IFN-γ), interleukin (IL)-12, IL-4, IL-10, and IL-17A. Results: A total of 686 differential genes, comprising 446 upregulated and 240 down regulated genes, were identified. The enrichment of KEGG pathway revealed that the majority of differential genes were enriched in the T helper (Th1)/Th2 cell and Th17 cell differentiation pathways. In patients with sepsis, correlation analysis revealed a negative correlation between IL2RB and APACHE II score, SOFA score, CRP, and PCT. IFN-γ and IL-12 levels were elevated in PBMC of septic patients after IL2RB transfection, but IL-4, IL-10, and IL-17A levels were lowered. Conclusion: Sepsis-induced immunological dysfunction is improved by IL2RB, which also balances Th1/Th2 responses and prevents Th17 activation.

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Anisomycin protects against sepsis by attenuating IκB kinase-dependent NF-κB activation and inflammatory gene expression

Cited by 8 publications

References 16 publications

MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils

MCC950 improves lipopolysaccharide‑induced systemic inflammation in mice by relieving pyroptosis in blood neutrophils

Anti-Inflammatory Effects of Idebenone Attenuate LPS-Induced Systemic Inflammatory Diseases by Suppressing NF-κB Activation

IL2RB affects Th1/Th2 and Th17 responses of peripheral blood mononuclear cells from septic patients

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