ArticleBritish journal of pharmacology2016
Neutrophil elastase induces inflammation and pain in mouse knee joints via activation of proteinase-activated receptor-2.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Prevalence of osteoarthritis in individuals with COPD: a systematic review.International journal of chronic obstructive pulmonary diseasePooled it
- Characterization of a mouse model to study mechanisms of hemophilia A pain.Blood advances · 2026Article
- Psoriasis patients with psoriatic arthritis demonstrate a reduced regulatory capacity for neutrophil elastase.Rheumatology (Oxford, England) · 2026Article
- The role of neutrophils in the pathophysiology of knee osteoarthritis : a review.Bone & joint research · 2026Article
- Lgmn targets two distinct GPCRs, PAR2 and µ-OR1, and induces cell death in acute lymphoblastic leukemia through an intracellular Ca²⁺ imbalance triggered by ER Ca²⁺ release.Cell death discovery · 2026Article
- Modulation of Nociceptive Ion Channels by Protease-Activated Receptor-2 in Inflammatory Pain: Molecular Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Trypsin inhibitor isolated from the seeds of Inga laurina (sw.) Willd decreased inflammatory and nociceptive responses in mice.Inflammopharmacology · 2025Article
- Harnessing mesenchymal stem/stromal cells-based therapies for rheumatoid arthritis: mechanisms, clinical applications, and microenvironmental interactions.Stem cell research & therapy · 2025Review
- Effect of sivelestat on postoperative outcomes in patients with acute type A aortic dissection and hypoxemia: a retrospective analysis.American journal of cardiovascular disease · 2025Article
- Neural and immune roles in osteoarthritis pain: Mechanisms and intervention strategies.Journal of orthopaedic translation · 2024Review
- Article
- Neutrophils in Inflammatory Bone Diseases.Current osteoporosis reports · 2024Review
- Infusion of GMSCs relieves autoimmune arthritis by suppressing the externalization of neutrophil extracellular traps via PGE2-PKA-ERK axis.Journal of advanced research · 2024Article
- Sivelestat (Neutrophil Elastase Inhibitor) as an Anti-inflammatory and Anti-viral Agent: An In Silico Study.Cureus · 2024Article
- Neutrophils in Inflammatory Diseases: Unraveling the Impact of Their Derived Molecules and Heterogeneity.Cells · 2023Review
- Isolation and Characterization of Poeciguamerin, a Peptide with Dual Analgesic and Anti-Thrombotic Activity from theInternational journal of molecular sciences · 2023Article
- C781, a β-Arrestin Biased Antagonist at Protease-Activated Receptor-2 (PAR2), Displays in vivo Efficacy Against Protease-Induced Pain in Mice.The journal of pain · 2023Article
- Identification of Key Diagnostic Markers and Immune Infiltration in Osteoarthritis.Combinatorial chemistry & high throughput screening · 2023Article
- GB83, an Agonist of PAR2 with a Unique Mechanism of Action Distinct from Trypsin and PAR2-AP.International journal of molecular sciences · 2022Article
- Impact of habitual chewing on gut motility via microbiota transition.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
background and purposeNeutrophil elastase plays a crucial role in arthritis. Here, its potential in triggering joint inflammation and pain was assessed, and whether these effects were mediated by proteinase-activated receptor-2 (PAR2). EXPERIMENTAL APPROACH: Neutrophil elastase (5 μg) was injected into the knee joints of mice and changes in blood perfusion, leukocyte kinetics and paw withdrawal threshold were assessed. Similar experiments were performed in animals pretreated with the neutrophil elastase inhibitor sivelestat, the PAR2 antagonist GB83, the p44/42 MAPK inhibitor U0126 and in PAR2 receptor knockout (KO) mice. Neutrophil elastase activity was also evaluated in arthritic joints by fluorescent imaging and sivelestat was assessed for anti-inflammatory and analgesic properties. KEY
resultsIntra-articular injection of neutrophil elastase caused an increase in blood perfusion, leukocyte kinetics and a decrease in paw withdrawal threshold. Sivelestat treatment suppressed this effect. The PAR2 antagonist GB83 reversed neutrophil elastase-induced synovitis and pain and these responses were also attenuated in PAR2 KO mice. The MAPK inhibitor U0126 also blocked neutrophil elastase-induced inflammation and pain. Active neutrophil elastase was increased in acutely inflamed knees as shown by an activatable fluorescent probe. Sivelestat appeared to reduce neutrophil elastase activity, but had only a moderate anti-inflammatory effect in this model. CONCLUSIONS AND IMPLICATIONS: Neutrophil elastase induced acute inflammation and pain in knee joints of mice. These changes are PAR2-dependent and appear to involve activation of a p44/42 MAPK pathway. Blocking neutrophil elastase, PAR2 and p44/42 MAPK activity can reduce inflammation and pain, suggesting their utility as therapeutic targets.
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Registered trials
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.