Role of alpha1-acid glycoprotein in therapeutic antifibrotic effects of imatinib with macrolides in mice.

Role of alpha1-acid glycoprotein in therapeutic antifibrotic effects of imatinib with macrolides in mice. Research Abstract Details 

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Role of alpha1-acid glycoprotein in therapeutic antifibrotic effects of imatinib with macrolides in mice. Abstract Text:

Momoyo Azuma,Yasuhiko Nishioka,Yoshinori Aono,Mami Inayama,Hideki Makino,Jun Kishi,Masayuki Shono,Katsuhiro Kinoshita,Hisanori Uehara,Fumitaka Ogushi,Keisuke Izumi,Saburo Sone,Momoyo Azuma,Yasuhiko Nishioka,Yoshinori Aono,Mami Inayama,Hideki Makino,Jun Kishi,Masayuki Shono,Katsuhiro Kinoshita,Hisanori Uehara,Fumitaka Ogushi,Keisuke Izumi,Saburo Sone,

RATIONALE: Imatinib is an inhibitor of platelet-derived growth factor receptors. We have reported that treatment with imatinib inhibited bleomycin-induced pulmonary fibrosis in mice. However, late treatment with imatinib had no effect. OBJECTIVES: To clarify why imatinib had no antifibrotic effect when its administration was delayed, we focused on alpha(1)-acid glycoprotein (AGP), because it was reported to bind imatinib and mediate drug resistance. METHODS: The concentration of AGP in serum of mice and patients with idiopathic pulmonary fibrosis was measured by radial immunodiffusion testing. The effects of AGP in vitro were evaluated by assaying the growth of lung fibroblasts. We examined the combined effects of erythromycin (EM) or clarithromycin (CAM) on bleomycin-induced pulmonary fibrosis in mice. MEASUREMENTS AND MAIN RESULTS: Addition of AGP abrogated imatinib-mediated inhibition of the growth of fibroblasts. However, treatment with EM or CAM restored the growth-inhibitory effects of imatinib. The elevated level of AGP was detected in serum and lung homogenates in bleomycin-exposed mice and reached a plateau on Day 14. Imatinib alone did not ameliorate pulmonary fibrosis when treatment was started on Day 15, whereas coadministration of imatinib and EM or CAM significantly reduced the fibrogenesis via inhibition of the growth of fibroblasts in vivo. Serum levels of AGP were higher in patients with idiopathic pulmonary fibrosis than in healthy subjects. CONCLUSIONS: AGP is an important regulatory factor modulating the ability of imatinib to prevent pulmonary fibrosis in mice, and combined therapy with imatinib and EM or CAM might be useful for treatment of pulmonary fibrosis.

Role of alpha1-acid glycoprotein in therapeutic antifibrotic effects of imatinib with macrolides in mice. Publishing Authors By Initials

M Azuma,Y Nishioka,Y Aono,M Inayama,H Makino,J Kishi,M Shono,K Kinoshita,H Uehara,F Ogushi,K Izumi,S Sone,M Azuma,Y Nishioka,Y Aono,M Inayama,H Makino,J Kishi,M Shono,K Kinoshita,H Uehara,F Ogushi,K Izumi,S Sone,

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

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Role of alpha1-acid glycoprotein in therapeutic antifibrotic effects of imatinib with macrolides in mice. Journal Published:

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

Journal: American journal of respiratory and critical care

VOLUME: 176

Page Numbers: 1243-50

Journal Abbreviation: Am. J. Respir. Crit. Care Med.

ISSN: 1535-4970

DAY: 23

MONTH: 08

YEAR: 2007

Role of alpha1-acid glycoprotein in therapeutic antifibrotic effects of imatinib with macrolides in mice. Information

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LANGUAGE: eng

NlmUniqueID: 9421642

Role of alpha1-acid glycoprotein in therapeutic antifibrotic effects of imatinib with macrolides in mice. Keywords Mesh Terms:

KEYWORDS: Pyrimidines

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Role of alpha1-acid glycoprotein in therapeutic antifibrotic effects of imatinib with macrolides in mice. Information

Substance Name: Clarithromycin

Registry Number: 81103-11-9

Grant and Affiliation Information for Role of alpha1-acid glycoprotein in therapeutic antifibrotic effects of imatinib with macrolides in mice.

AFFILIATION: Department of Internal Medicine and Molecular Therapeutics, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.

Country: United States

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MEDLINETA: Am J Respir Crit Care Med

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