ArticleScientific reports2017
JNK Activation Turns on LPS- and Gram-Negative Bacteria-Induced NADPH Oxidase-Dependent Suicidal NETosis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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Who cites it
121 citing papers in PubMed, 173 citations in OpenAlex.
- Review
- Recent Advances in Fluorescent Probes for Imaging Enzyme Activity in NETosis.Chembiochem : a European journal of chemical biology · 2026Review
- Redox-modulation of regulated cell death: implications for synergistic anticancer therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Impact of Neutrophil Extracellular Traps on Clinical Outcome after Subarachnoid Hemorrhage: A Translational Narrative Review.Translational stroke research · 2026Review
- Dual inhibition of neutrophil superoxide generation and elastase releaseRSC advances · 2026Article
- PP4 modulates macrophage-neutrophil crosstalk to restrict CCL5 -driven NETosis in sepsis.Redox biology · 2026Article
- The Interaction of Neutrophil Extracellular Traps and Complement in Intracerebral Hemorrhage.Cellular and molecular neurobiology · 2026Review
- Targeting Neutrophil Extracellular Traps: A New Strategy for the Treatment of Acute Ischemic Stroke Based on Thrombolysis Resistance.Seminars in thrombosis and hemostasis · 2026Review
- Mitochondria as Inducers of Neutrophil Extracellular Traps.Inflammation · 2026Review
- The hormone-microbiota-NET framework in gynecologic diseases: evidence, controversies, and translational opportunities.Frontiers in immunology · 2026Review
- Neutrophil Extracellular Traps in Pancreatic Ductal Adenocarcinoma: A Vicious Cycle in the Tumor Microenvironment and Targeted Interventions.International journal of biological sciences · 2026Review
- Modified Dachengqi Decoction ameliorates sepsis-induced lung injury via the gut microbiota-bile acid axis.Frontiers in cellular and infection microbiology · 2026Article
- Reactive sulfur species as emerging immunomodulators: mechanistic insights and therapeutic prospects.Frontiers in immunology · 2026Review
- One trigger, two fates: hemolysate shapes neutrophil extracellular traps (NETs) formation in a context-dependent manner.Frontiers in immunology · 2026Article
- Desloratadine as the selective 5HTJournal of neuroinflammation · 2025Article
- Next-Generation Regenerative Therapies for Alpha-1 Antitrypsin Deficiency: Molecular Pathogenesis to Clinical Translation.International journal of molecular sciences · 2025Review
- Review
- Single-cell atlas of human gingiva unveils a NETs-related neutrophil subpopulation regulating periodontal immunity.Journal of advanced research · 2025Article
- A Web of Challenges: The Therapeutic Struggle to Target NETs in Disease.International journal of molecular sciences · 2025Review
- Gingival inflammation and leukocyte-endothelium cell interactions in women with polycystic ovary syndrome.Journal of periodontology · 2025Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Neutrophils cast neutrophil extracellular traps (NETs) to ensnare microbial pathogens. Nevertheless, the molecular rheostats that regulate NETosis in response to bacteria are not clearly established. We hypothesized that stress-activated protein kinase or c-Jun N-terminal Kinase (SAPK/JNK) is a molecular switch that turns on NETosis in response to increasing concentrations of lipopolysaccharide (LPS)- and Gram-negative bacteria. Here we show that Escherichia coli LPS (0111:B4; 10-25 μg/ml), but not phorbol myristate acetate (PMA), activates JNK in human neutrophils in a dose-dependent manner. JNK inhibitors SP600125 and TCSJNK6o, and a TLR4 inhibitor TAK242 suppress reactive oxygen species production and NETosis in LPS-, but not PMA-treated neutrophils. Diphenyleneiodonium suppresses LPS-induced NETosis, confirming that endotoxin induces NADPH oxidase-dependent NETosis. Immunoblots, Sytox Green assays, and confocal microscopy of cleaved caspase-3 and nuclear morphology show that JNK inhibition does not induce apoptosis in LPS-stimulated neutrophils. JNK inhibition also suppresses NETosis induced by two typical Gram-negative bacteria, E. coli and Pseudomonas aeruginosa. Therefore, we propose that neutrophils use a TLR4-dependent, JNK-mediated molecular sensing mechanism to initiate NADPH oxidase-dependent suicidal NETosis in response to increasing concentrations of LPS, and Gram-negative bacteria. The LPS-TLR4-JNK activation axis determines the fate of these cells: to be or not to be NETotic neutrophils.
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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.