Regulation of lipid metabolism in macrophages by methotrexate
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概要
- 論文の詳細を見る
Objective : Methotrexate (MTX) is widely used for the treatment of rheumatoid arthritis (RA). It has been demonstrated that MTX can reduce the mortality rate of RA patients by decreasing events related to atherosclerotic cardiovascular disease. In order to investigate the mechanism of this preventive effect of MTX, we evaluated its influence on the expression and function of CD36, peroxisome proliferator-activated receptor-gamma (PPARγ), liver X receptor alpha (LXRα), ATP-binding cassette transporter A1 (ABCA1), and cholesterol uptake and efflux. Methods : Human monocytic THP-1 cells were incubated with various concentrations of MTX for indicated periods. Expression of CD36 was determined by flow cytometry and gene expression of CD36, PPARγ, LXRα , and ABCA1 was determined by reverse transcription PCR. In order to evaluate the effect of MTX on cholesterol uptake and efflux, THP-1 cells were incubated with MTX and isotope-labeled cholesterol followed by co-incubation with high-density lipoprotein (HDL) cholesterol or apolipoprotein A-I (apoA-I). Results : At clinically relevant concentrations, MTX significantly induced the expression of genes for these lipid metabolism-associated molecules in THP-1 cells. MTX significantly increased cholesterol uptake by THP-1 cells, and also enhanced cholesterol release from these cells to HDL cholesterol and apoA-I. Conclusion : These findings suggest that MTX might be able to prevent the progression of atherosclerosis in RA patients by modulating macrophage lipid metabolism.
- 北里大学の論文
- 2005-09-30
著者
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Kondo Hirobumi
Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine
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Kondo Hirobumi
Departments Of Internal Medicine And Pathology Kitasato University School Of Medicine
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Kondo H
Kitasato Univ. School Of Medicine
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Kondo Hirobumi
Department Of Internal Medicine Kitasato Institute Medical Center Hospital
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AKAHOSHI Tohru
Departments of Laboratory Medicine, Kitasato University School of Medicine
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WATABE Hiroyuki
Department of Internal Medicine, Kitasato University School of Medicine
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Akahoshi T
Departments Of Internal Medicine And Pathology Kitasato University School Of Medicine
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Akahoshi Tohru
Department Of Clinical Pathology Kitasato University School Of Medicine
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Watabe Hiroyuki
Department Of Biochemistry Faculty Of Pharmaceutical Sciences Health Sciences University Of Hokkaido
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Watabe Hiroyuki
Department Of Rheumatology And Infectious Diseases Kitasato University School Of Medicine
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Akahoshi Tohru
Department Of Internal Medicine Kitasato University School Of Medicine
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Watabe Hiroyuki
Department of Applied Chemistry, Faculty of Engineering, Yamagata University
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