Effect of hypoxia on the expression of fractalkine in human endothelial cells.
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-gamma (IFN-gamma) in endothelial cells. Human umbilical vein endothelial cells were cultured, and the stimulation of the cells with IFN-gamma was found to induce the expression of fractalkine. Hypoxia inhibited the expression of fractalkine mRNA and protein by IFN-gamma, 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-gamma. 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.
Yamashita
Koji
K
Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan.
Imaizumi
Tadaatsu
T
Hatakeyama
Masaharu
M
Tamo
Wakako
W
Kimura
Daisuke
D
Kumagai
Mika
M
Yoshida
Hidemi
H
Satoh
Kei
K
D000111:Acetylcysteine / Q000494:pharmacology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics / Q000378:metabolism*; D003676:Deferoxamine / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D007502:Iron Chelating Agents; D008565:Membrane Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D007371:Interferon-gamma; D003676:Deferoxamine; D010100:Oxygen; D000111:Acetylcysteine