Role of regulatory T cells in atheroprotective effects of granulocyte colony-stimulating factor

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• 作者：Raita Uchiyama^a ; ¹ ; Hiroshi Hasegawa^a ; ¹ ; Yoshihito Kameda^a ; Kazutaka Ueda^a ; Yoshio Kobayashi^a ; Issei Komuro^b ; Hiroyuki Takano^c ; ^{htakano-cib@umin.ac.jp}
• 关键词：Atherosclerosis ; Regulatory T cells ; G-CSF ; Cytokine ; Foxp3
• 刊名：Journal of Molecular and Cellular Cardiology
• 出版年：2012
• 期刊代码：171_00222828
• 类别：bio
• 出版时间：May, 2012
• 卷：52
• 期：5
• 页码：1038-1047
• 文件大小：1312 K

摘要

We and others have previously reported that granulocyte colony-stimulating factor (G-CSF) prevents left ventricular remodeling and dysfunction after myocardial infarction in animal models and human. We have also reported that G-CSF inhibits the progression of atherosclerosis in animal models, but its precise mechanism is still elusive. So, we examined the effects of G-CSF on atherosclerosis in apolipoprotein E-deficient (ApoE^{鈭?鈭?/sup>) mice. Twelve-week-old male ApoE鈭?鈭?/sup> mice were subcutaneously administrated with 200 渭g/kg of G-CSF or saline once a day for 5 consecutive days per a week for 4 weeks. Atherosclerotic lesion of aortic sinus was significantly reduced in the G-CSF-treated mice compared with the saline-treated mice (35%reduction, P < 0.05). G-CSF significantly reduced the expression level of interferon-纬 by 31%and increased the expression level of interleukin-10 by 20%in atherosclerotic lesions of aortic sinus. G-CSF increased the number of CD4+CD25+ regulatory T cells in lymph nodes and spleen, and enhanced the suppressive function of regulatory T cells in vitro. G-CSF markedly increased the number of Foxp3-positive regulatory T cells in atherosclerotic lesions of aortic sinus. Administration of anti-CD25 antibody (PC61) that depletes regulatory T cells abrogated these atheroprotective effects of G-CSF. Moreover, in ApoE鈭?鈭?/sup>/CD28鈭?鈭?/sup> mice, that lack regulatory T cells, the protective effects of G-CSF on atherosclerosis were not recognized. These findings suggest that regulatory T cells play an important role in the atheroprotective effects of G-CSF.}