Tohoku J. Exp. Med., 2003, 200 (4)

Effect of Hypoxia on the Expression of Fractalkine
in Human Endothelial Cells

KOJI YAMASHITA, TADAATSU IMAIZUMI, MASAHARU HATAKEYAMA, WAKAKO TAMO,
DAISUKE KIMURA,¹ MIKA KUMAGAI, HIDEMI YOSHIDA and KEI SATOH

Department of Vascular Biology, Institute of Brain Science, and ¹The First Department of Surgery, Hirosaki University School of Medicine, Hirosaki 036-8562

CX3CL1/fractalkine is a chemokine with a unique CX3C motif. Hypoxia mediates the expression of various genes, such as vascular endothelial growth factor (VEGF), cyclooxygenase-2, and plasminogen-activator inhibitor-1, in vascular endothelial cells. We studied the effect of hypoxia on the expression of fractalkine induced by interferon-γ (IFN-γ) in endothelial cells. Human umbilical vein endothelial cells were cultured, and the stimulation of the cells with IFN-γ was found to induce the expression of fractalkine. Hypoxia inhibited the expression of fractalkine mRNA and protein by IFN-γ, and this effect was observed with concomitant increase in VEGF expression. Desferrioxamine, an iron chelator that mimics hypoxia in vitro, also inhibited the fractalkine production induced by IFN-γ. Hypoxia did not affect the degradation of fractalkine mRNA. The inhibition of fractalkine expression by hypoxia was reversed on returning the cultures to reoxygenation condition. Inhibition of IFN-induced fractalkine expression by hypoxia was not affected by the presence of a radical scavenger, N-acetyl-L-cysteine, and the involvement of reactive oxygen species may be excluded. Inhibition of fractalkine expression by hypoxia may be involved in the pathophysiology of ischemic diseases.

keywords —— hypoxia; fractalkine; endothelial cells

© 2003 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2003, 200, 187-194

Address for reprints: Tadaatsu Imaizumi, Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, 5 Zaifucho, Hirosaki 036-8562, Japan.

e-mail: timaizum@cc.hirosaki-u.ac.jp