ArticleInternational journal of molecular sciences2022
Inhibition of Netosis with PAD Inhibitor Attenuates Endotoxin Shock Induced Systemic Inflammation.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- The TG2/LRP1 Pathway for T Cell Activation by Post-Translationally Modified Antigens.Immunological reviews · 2026Review
- Evolution of neutrophil extracellular traps in the pathology of stroke.Neural regeneration research · 2026Article
- Epigenetics-mediated pathological alterations and their diagnostic and therapeutic potential in sepsis-associated acute kidney injury.Clinical epigenetics · 2026Review
- The Role of Neutrophil Extracellular Traps (NETs) in the Pathogenesis of Ovarian Cancer: New Insight and Future Perspectives.Molecular biotechnology · 2026Review
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- Sepsis-induced coagulopathy: recent insights on the role and clinical application of neutrophil extracellular trap formation.Scientific reports · 2025Article
- Cell-free DNA in sepsis: from molecular insights to clinical management.Military Medical Research · 2025Review
- NETs in ovarian cancer progression: innovative nanoparticle-based therapeutic strategies.European journal of medical research · 2025Review
- Targeting PAD4: A Promising Strategy to Combat β-Cell Loss in Type 1 Diabetes.International journal of molecular sciences · 2025Article
- Crossing epigenetic frontiers: the intersection of novel histone modifications and diseases.Signal transduction and targeted therapy · 2024Review
- Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directions.Frontiers in immunology · 2024Review
- Citrullination and the protein code: crosstalk between post-translational modifications in cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Role of Peptidylarginine Deiminase 4 in Central Nervous System Diseases.Molecular neurobiology · 2023Review
- Lipid Metabolism Reprogramming of Immune Cells in Acne: An Update.Clinical, cosmetic and investigational dermatology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Neutrophils play a pivotal role in innate immunity by releasing neutrophils extracellular traps (NETs). Excessive NETs are detrimental to the local tissue and further exacerbate inflammation. Protein arginine deiminases (PAD) mediate histone citrullination and NET formation that, in turn, exacerbate endotoxin shock damages. In this study, we further investigated the molecular mechanism underlying PAD and NETs in endotoxic stress in mice. The control group mice were injected with solvent, the LPS endotoxic shock group mice were intraperitoneally injected with LPS at 35 mg/kg only, while the LPS and PAD inhibitor YW3-56 treatment group mice were injected with YW3-56 at 10 mg/kg prior to the LPS injection. YW3-56 significantly prolonged the survival time of the LPS-treated mice. NETs, cfDNA, and inflammatory factors were detected by ELISA in serum, paitoneal cavity, and lung at 24 h after LPS administration. Lung injuries were detected by immunostaining, and lung tissue transcriptomes were analyzed by RNA-seq at 24 h after LPS administration. We found that YW3-56 altered neutrophil tissue homeostasis, inhibited NET formation, and significantly decreased cytokines (IL-6, TNFα and IL-1β) levels, cytokines gene expression, and lung tissue injury. In summary, NET formation inhibition offers a new avenue to manage inflammatory damages under endotoxic stress.
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