CXCR1 and CXCR2 Inhibition by Ladarixin Improves Neutrophil-Dependent Airway Inflammation in Mice

dc.creatorMattos, Matheus Silverio
dc.creatorFerrero, Maximiliano Ruben
dc.creatorKraemer, Lucas
dc.creatorLopes, Gabriel Augusto Oliveira
dc.creatorReis, Diego Carlos
dc.creatorCassali, Geovanni Dantas
dc.creatorOliveira, Fabrício Marcus Silva
dc.creatorBrandolini, Laura
dc.creatorAllegretti, Marcello
dc.creatorGarcia, Cristiana Couto
dc.creatorMartins, Marco Aurélio
dc.creatorTeixeira, Mauro Martins
dc.creatorRusso, Remo Castro
dc.date2021-01-02T18:05:26Z
dc.date2021-01-02T18:05:26Z
dc.date2020
dc.date.accessioned2023-09-26T20:18:25Z
dc.date.available2023-09-26T20:18:25Z
dc.identifierMATTOS, Matheus Silverio et al. CXCR1 and CXCR2 Inhibition by Ladarixin Improves Neutrophil-Dependent Airway Inflammation in Mice. Frontiers in Immunology, v. 11, Article 566953, p. 1-22, Oct. 2020.
dc.identifier1664-3224
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/45487
dc.identifier10.3389/fimmu.2020.566953
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8853834
dc.descriptionRationale: Increased IL-8 levels and neutrophil accumulation in the airways are common features found in patients affected by pulmonary diseases such as Asthma, Idiopathic Pulmonary Fibrosis, Influenza-A infection and COPD. Chronic neutrophilic inflammation is usually corticosteroid insensitive and may be relevant in the progression of those diseases. Objective: To explore the role of Ladarixin, a dual CXCR1/2 antagonist, in several mouse models of airway inflammation with a significant neutrophilic component. Findings: Ladarixin was able to reduce the acute and chronic neutrophilic influx, also attenuating the Th2 eosinophil-dominated airway inflammation, tissue remodeling and airway hyperresponsiveness. Correspondingly, Ladarixin decreased bleomycin-induced neutrophilic inflammation and collagen deposition, as well as attenuated the corticosteroid resistant Th17 neutrophil-dominated airway inflammation and hyperresponsiveness, restoring corticosteroid sensitivity. Finally, Ladarixin reduced neutrophilic airway inflammation during cigarette smoke-induced corticosteroid resistant exacerbation of Influenza-A infection, improving lung function and mice survival. Conclusion: CXCR1/2 antagonist Ladarixin offers a new strategy for therapeutic treatment of acute and chronic neutrophilic airway inflammation, even in the context of corticosteroid-insensitivity.
dc.formatapplication/pdf
dc.languageeng
dc.publisherFrontiers Media
dc.rightsopen access
dc.subjectNeutrófilos (PMNs)
dc.subjectAsma
dc.subjectFibrose
dc.subjectDoença pulmonar obstrutiva crônica
dc.subjectInfluenza A (H1N1)
dc.subjectNeutrophils (PMNs)
dc.subjectAsthma
dc.subjectFibrosis
dc.subjectChronic obstructive pulmonary disease
dc.subjectInfluenza A (H1N1)
dc.titleCXCR1 and CXCR2 Inhibition by Ladarixin Improves Neutrophil-Dependent Airway Inflammation in Mice
dc.typeArticle


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