ArticleBritish journal of pharmacology2008
Treatment with DF 2162, a non-competitive allosteric inhibitor of CXCR1/2, diminishes neutrophil influx and inflammatory hypernociception in mice.
Article in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 97 citations in OpenAlex.
- Protectin DX reduces inflammatory pain initiated by superoxide anion in mice: targeting leukocyte recruitment, oxidative stress, cytokine production and TRPV1Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 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
- Platelet-derived microvesicles modulate the bioenergetic and inflammatory phenotype of human polymorphonuclear leukocytes.Journal of leukocyte biology · 2025Article
- CXCL6 Reshapes Lipid Metabolism and Induces Neutrophil Extracellular Trap Formation in Cholangiocarcinoma Progression and Immunotherapy Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CXCL7 enhances RANKL-induced osteoclastogenesis via the activation of ERK/NFATc1 signaling pathway in inflammatory arthritis.Arthritis research & therapy · 2025Article
- Exploring the role of neutrophils in inflammatory pain hypersensitivity via single-cell transcriptome profiling.Frontiers in immunology · 2025Article
- Therapeutic inhibition of CXCR1/2: where do we stand?Internal and emergency medicine · 2023Review
- The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.Cellular & molecular immunology · 2023Review
- Chemokines and chemokine receptors as promising targets in rheumatoid arthritis.Frontiers in immunology · 2023Review
- Emerging Approaches for the Management of Chemotherapy-Induced Peripheral Neuropathy (CIPN): Therapeutic Potential of the C5a/C5aR Axis.Pain and therapy · 2022Review
- Low-Density Granulocytes in Immune-Mediated Inflammatory Diseases.Journal of immunology research · 2022Review
- CXCR1 and its downstream NF-κB inflammation signaling pathway as a key target of Guanxinning injection for myocardial ischemia/reperfusion injury.Frontiers in immunology · 2022Article
- Inflammation-Independent Antinociceptive Effects of DF2755A, a CXCR1/2 Selective Inhibitor: A New Potential Therapeutic Treatment for Peripheral Neuropathy Associated to Non-Ulcerative Interstitial Cystitis/Bladder Pain Syndrome.Frontiers in pharmacology · 2022Article
- Neutrophils in the Pathogenesis of Rheumatoid Arthritis and Systemic Lupus Erythematosus: Same Foe Different M.O.Frontiers in immunology · 2021Review
- MicroLet-7b Regulates Neutrophil Function and Dampens Neutrophilic Inflammation by Suppressing the Canonical TLR4/NF-κB Pathway.Frontiers in immunology · 2021Article
- Novel 1,3,4-Oxadiazole Derivatives of Pyrrolo[3,4-International journal of molecular sciences · 2020Article
- Effects of immune cell-targeted treatments result from the suppression of neuronal oxidative stress and inflammation in experimental diabetic rats.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- The role of neutrophils in neuro-immune modulation.Pharmacological research · 2020Review
- Rheumatoid Arthritis Synovial Fluid Neutrophils Drive Inflammation Through Production of Chemokines, Reactive Oxygen Species, and Neutrophil Extracellular Traps.Frontiers in immunology · 2020Article
- Chemokine Signaling in Chemotherapy-Induced Neuropathic Pain.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeNeutrophil migration into tissues is involved in the genesis of inflammatory pain. Here, we addressed the hypothesis that the effect of CXC chemokines on CXCR1/2 is important to induce neutrophil migration and inflammatory hypernociception. EXPERIMENTAL APPROACH: Mice were treated with a non-competitive allosteric inhibitor of CXCR1/2, DF 2162, and neutrophil influx and inflammatory hypernociception were assessed by myeloperoxidase assay and electronic pressure meter test, respectively, in various models of inflammation. KEY
resultsDF 2162 inhibited neutrophil chemotaxis induced by CXCR1/2 ligands but had no effect on CXCL8 binding to neutrophils. A single mutation of the allosteric site at CXCR1 abrogated the inhibitory effect of DF 2162 on CXCL-8-induced chemotaxis. Treatment with DF 2162 prevented influx of neutrophils and inflammatory hypernociception induced by CXCL1 in a dose-dependent manner. The compound inhibited neutrophil influx and inflammatory hypernociception induced by carrageenan, lipopolysaccharide and zymosan, but not hypernociception induced by dopamine and PGE(2). DF 2162 had a synergistic effect with indomethacin or the absence of TNFR1 to abrogate carrageenan-induced hypernociception. Treatment with DF 2162 diminished neutrophil influx, oedema formation, disease score and hypernociception in collagen-induced arthritis. CONCLUSIONS AND IMPLICATIONS: CXCR1/2 mediates neutrophil migration and is involved in the cascade of events leading to inflammatory hypernociception. In addition to modifying fundamental pathological processes, non-competitive allosteric inhibitors of CXCR1/2 may have the additional benefit of providing partial relief for pain and, hence, may be a valid therapeutic target for further studies aimed at the development of new drugs for the treatment of rheumatoid arthritis.
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