ArticleMucosal immunology2014
Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung.
Article in Mucosal immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 82 citations in OpenAlex.
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- Eupatilin modulates the Mcl-1 ubiquitination status and PI3K/Akt/Foxo3a pathway to inhibit apoptosis and alleviate sepsis-induced acute myocardial injury.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- ALX/FPR2 Receptor Activation by Inflammatory (fMLFII) and Pro-resolving (LXAACS physical chemistry Au · 2025Article
- Temporal dichotomy of neutrophil function in acute liver injury and repair.JHEP reports : innovation in hepatology · 2025Article
- Drug repurposing of cyclin-dependent kinase inhibitors for neutrophilic acute respiratory distress syndrome and psoriasis.Journal of advanced research · 2025Review
- Inhibition of DYRK1B BY C81 impedes inflammatory processes in leukocytes by reducing STAT3 activity.Cellular and molecular life sciences : CMLS · 2025Article
- Cell Death and Infection: Implications for Host and Microbe.Advances in experimental medicine and biology · 2025Review
- Apoptotic Vesicles Attenuate Acute Lung InjuryInternational journal of nanomedicine · 2025Article
- 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
- Sepsis in elderly patients: the role of neutrophils in pathophysiology and therapy.Internal and emergency medicine · 2024Review
- Neutrophils facilitate the epicardial regenerative response after zebrafish heart injury.Developmental biology · 2024Article
- Inflammatory signalling in atrial cardiomyocytes: a novel unifying principle in atrial fibrillation pathophysiology.Nature reviews. Cardiology · 2023Review
- Delayed neutrophil apoptosis may enhance NET formation in ARDS.Respiratory research · 2022Article
- Resolution-promoting autacoids demonstrate promising cardioprotective effects against heart diseases.Molecular biology reports · 2022Review
- Selective Cdk9 inhibition resolves neutrophilic inflammation and enhances cardiac regeneration in larval zebrafish.Development (Cambridge, England) · 2022Article
- Targeting Neutrophils for Promoting the Resolution of Inflammation.Frontiers in immunology · 2022Review
- Inhibition of Cyclin-Dependent Kinase 9 Downregulates Cytokine Production Without Detrimentally Affecting Human Monocyte-Derived Macrophage Viability.Frontiers in cell and developmental biology · 2022Article
- The multiple mechanisms of MCL1 in the regulation of cell fate.Communications biology · 2021Review
- Anti-TNF-α agents Modulate SARS-CoV-2 Receptors and Increase the Risk of Infection Through Notch-1 Signaling.Frontiers in immunology · 2021Article
- Src kinase inhibition with dasatinib impairs neutrophil function and clearance of Escherichia coli infection in a murine model of acute lung injury.Journal of inflammation (London, England) · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (Ri) from 19 to 7 h and improved organ dysfunction with enhanced alveolar-capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (Ri; 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation.
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