Effect of imatinib on airway smooth muscle thickening in a murine model of chronic asthma

Int Arch Allergy Immunol. 2011;155(3):243-51. doi: 10.1159/000321261. Epub 2011 Feb 2.


Background: Asthma is characterized by airway hyperresponsiveness (AHR), inflammation and remodeling. The tyrosine kinase inhibitor imatinib mesylate was developed to inhibit BCR-ABL kinase activity; however, it also has potent inhibitory activity against the c-Kit and platelet-derived growth factor receptors. The present study aimed to determine whether imatinib suppresses airway smooth muscle (ASM) remodeling and whether its effect is associated with growth factors such as transforming growth factor (TGF)-β1 and stem cell factor (SCF).

Methods: We developed a mouse model of airway remodeling, which includes smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated with imatinib during the OVA challenge.

Results: Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation and AHR compared with control mice. In addition, the mice chronically exposed to OVA developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of imatinib significantly inhibited the development of AHR, eosinophilic inflammation and, importantly, ASM remodeling in mice chronically exposed to OVA. Imatinib treatment significantly reduced the levels of interleukin-4, -5 and -13. In addition, TGF-β1 and SCF were significantly reduced in the imatinib-treated animals.

Conclusions: These results suggest that imatinib administration can prevent not only airway inflammation, but also airway remodeling associated with chronic allergen challenge. Imatinib may provide a clinically attractive therapy for chronic severe asthma.

MeSH terms

  • Airway Remodeling / drug effects*
  • Animals
  • Asthma / drug therapy*
  • Asthma / pathology
  • Benzamides
  • Chronic Disease
  • Female
  • Imatinib Mesylate
  • Interleukins / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / pathology
  • Ovalbumin / pharmacology
  • Piperazines / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Severity of Illness Index
  • Stem Cell Factor / biosynthesis
  • Transforming Growth Factor beta1 / biosynthesis


  • Benzamides
  • Interleukins
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Stem Cell Factor
  • Transforming Growth Factor beta1
  • Imatinib Mesylate
  • Ovalbumin