Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia.

Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia. Research Abstract Details 

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Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia. Abstract Text:

Kirsi Vuorinen,Fei Gao,Tim D Oury,Vuokko L Kinnula,Marjukka ,

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.

Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia. Publishing Authors By Initials

K Vuorinen,F Gao,TD Oury,VL Kinnula,M ,

For similar heterocyclic compounds: heterocyclic compounds, 1-ring: pyrimidines research abstracts see: heterocyclic compounds: heterocyclic compounds, 1-ring: pyrimidines research

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Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Experimental lung research

VOLUME: 33

Page Numbers: 357-73

Journal Abbreviation: Exp. Lung Res.

ISSN: 0190-2148

DAY: 3

MONTH: Sep

YEAR: 2007

Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8004944

Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia. Keywords Mesh Terms:

KEYWORDS: Pyrimidines

MESH TERMS: administration & dosage

Chemical & Substance for Abstract: Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia. Information

Substance Name: Protein-Tyrosine Kinases

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia.

AFFILIATION: Department of Medicine and Division of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Country: United States

AGENCY: United States NHLBI

GRANT: R01HL063700-05

ACRONYM: HL

MEDLINETA: Exp Lung Res

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