Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia

Exp Lung Res. 2007 Sep;33(7):357-73. doi: 10.1080/01902140701634827.


Profibrogeneic cytokines contribute to the accumulation of myofibroblasts in the lung interstitium in idiopathic pulmonary fibrosis (IPF). Imatinib mesylate, a tyrosine kinase inhibitor specific for Abl, platelet-derived growth factor receptor (PDGFR) and c-Kit tyrosine kinases, has been shown to inhibit fibrosis and profibrotic signaling in mouse models of inflammation-mediated lung reactions. The authors tested imatinib mesylate in vivo in a mouse model of crocidolite asbestos-induced progressive fibrosis. The ability of imatinib mesylate to inhibit profibrogeneic cytokine-induced human pulmonary fibroblast migration was tested in vitro and the expression of its target protein tyrosine kinases was assessed with immunofluorescence. In vivo, 10 mg/kg/day imatinib mesylate inhibited histological parenchymal fibrosis and led to a decrease in collagen deposition, but had no significant effect on asbestos-induced neutrophilia. However, 50 mg/kg/day imatinib mesylate did not inhibit collagen deposition. In vitro, IPF fibroblasts expressed Abl, PDGFR-alpha, PDGF-beta, but not c-Kit, and 1 microM imatinib mesylate inhibited profibrogeneic cytokine-induced IPF fibroblast migration. These results suggest that imatinib mesylate is a potential and specific inhibitor of fibroblast accumulation in asbestos-induced pulmonary fibrosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Apoptosis / drug effects
  • Asbestos, Crocidolite / toxicity*
  • Benzamides
  • Cell Culture Techniques
  • Cell Movement / drug effects
  • Cells, Cultured
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Humans
  • Imatinib Mesylate
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Piperazines* / administration & dosage
  • Pneumonia / chemically induced
  • Pneumonia / pathology
  • Pneumonia / prevention & control
  • Protein Kinase Inhibitors / administration & dosage
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / biosynthesis
  • Pulmonary Fibrosis / chemically induced
  • Pulmonary Fibrosis / physiopathology*
  • Pulmonary Fibrosis / prevention & control*
  • Pyrimidines* / administration & dosage


  • Antineoplastic Agents
  • Benzamides
  • Intercellular Signaling Peptides and Proteins
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Asbestos, Crocidolite
  • Imatinib Mesylate
  • Protein-Tyrosine Kinases