PURPOSE: The tyrosine kinase inhibitor imatinib and nilotinib were developed to inhibit BCR-ABL kinase activity. No data about the effect of nilotinib on chronic asthma is available. We aimed to see the effect of imatinib and nilotinib on airway smooth muscle in asthma.
METHODS: Murine model of chronic asthma was established by ovalbumin challenge. Imatinib and nilotinib were administrated daily by oral gavage for 3 months. Airway hyperresponsiveness, cytokine level, smooth muscle area, and the level of collagen were measured.
RESULTS: Imatinib and nilotinib treatment attenuated airway hyperresponsiveness. Total inflmmatory cell and eosinophil count were significantly lower in imatinib and nilotinib group. The level of IL-4, 5, 13, TGF-β1, and SCF were also lower in imatinib and nilotinib group, too. In hydroxyproline assay, the total collagen level was significantly lower in imatinib and nilotinib group. The quantification analysis showed that imatinib and nilotinib therapy significantly reduced the area of peribronchial α-smooth muscle actin staining.
CONCLUSIONS: Imatinib and nilotinib treatment reduced AHR and airway inflammations as well as remodeling (fibrosis and smooth muscle hyperplasia) in asthma.
CLINICAL IMPLICATIONS: This animal study suggests that imatinib and nilotinib can be used to treat asthma.
DISCLOSURE: The following authors have nothing to disclose: HyoungKyu Yoon, Chin Rhee
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