ArticleInternational journal of immunopathology and pharmacology
Anti-astmatic effect of ROCK inhibitor, GSK429286 A, in experimentally induced allergic airway inflammation.
Article in International journal of immunopathology and pharmacology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Inhibition of Rho-kinase restores impaired relaxation of airway smooth muscle in rat pups exposed to neonatal hyperoxia.Physiological reports · 2026Article
- Role of Rho-associated kinases and their inhibitor fasudil in neurodegenerative diseases.Frontiers in neuroscience · 2024Review
- Phenotypes and endotypes of cough in asthma.Therapeutic advances in respiratory diseaseReview
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10 authors.
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Abstract
backgroundAllergic asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, inflammation and remodeling. ROCK inhibitors have now been shown to have the potential to alleviate these symptoms, although the specific effects of a new ROCK inhibitor, GSK429286 A, remain underexplored.
objectiveThe aim of this study was to evaluate the therapeutic effects of a novel ROCK inhibitor, GSK429286 A, which exhibits a high affinity for both ROCK1 and ROCK2 isoforms, on allergic asthma in a guinea pig model, focusing on its effects on airway hyperresponsiveness, inflammation, and remodeling.
methodsTo induce allergic asthma, guinea pigs were sensitized with ovalbumin for 28 days, and in the middle of sensitization they were treated with different doses of the RoCK inhibitor, GSK429286 A. The study evaluated the effect of the administered doses on the reduction of airway hyperresponsiveness, by measuring specific airway resistance (sRaw), and the number of coughs after citric acid inhalation. We also monitored the anti-inflammatory effect by measuring levels of inflammatory cytokines, IL-2, IL-4, IL-5, IL-13, and remodeling markers, such as collagen deposition, and goblet cell hyperplasia. In addition, we monitored the possible anti-remodeling effect of GSK429286 A by histopathological examination.
resultsThe ROCK inhibitor, GSK429286 A, showed an effect on suppressing airway hyperresponsiveness by reducing sRaw and the number of coughs in treated guinea pigs compared to controls. Our investigated drug suppressed the release of key mediators of inflammation, including IL-2, IL-4, and IL-5, thus demonstrating the effect of this ROCK inhibitor on the suppression of inflammation in the airways. Finally, GSK429286 A reduced markers of airway remodeling such as collagen deposition and goblet cell hyperplasia.
conclusionGSK429286 A, an inhibitor of the ROCK pathway, exhibits significant anti-inflammatory and antiremodeling effects in a guinea pig model of allergic asthma. Indeed, we demonstrate its effect on suppressing airway hyperreactivity and reducing cough frequency. These findings suggest that GSK429286 A may be a promising therapeutic agent for allergic asthma, although further studies are needed to investigate its long-term efficacy, underlying mechanisms, and optimal dosing strategy.
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