Platelet-activating factor enhances the expression of vascular endothelial growth factor in normal human astrocytes.
Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular endothelial cells. To examine whether platelet-activating factor (PAF) induces the expression of VEGF in human astrocytes, we stimulated cultured normal astrocytes with PAF and performed semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) or real-time quantitative PCR for VEGF mRNA and enzyme-linked immunosorbent assay for VEGF protein. PAF increased the expression of VEGF in astrocytes in time- and dose-dependent manners. After 24-h stimulation, 10 nM PAF increased the levels of VEGF protein in astrocyte-conditioned medium by 1.3-fold. When the cells were subjected to hypoxia, the PAF-induced production of VEGF was enhanced by 6.7-fold as compared to the unstimulated cells incubated under normoxia. Dexamethasone was found to inhibit the enhanced VEGF production in response to the stimulation with PAF under hypoxia. We conclude that PAF induces VEGF gene expression in human astrocytes, and the PAF-induced increase in the expression of VEGF may modulate nervous tissue injury due to hypoxia.
Yoshida
Hidemi
H
Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan. hidemiyo@cc.hirosaki-u.ac.jp
Imaizumi
Tadaatsu
T
Tanji
Kunikazu
K
Matsumiya
Tomoh
T
Sakaki
Hirotaka
H
Kimura
Daisuke
D
Cui
Xue-Fan
XF
Kumagai
Mika
M
Tamo
Wakako
W
Shibata
Takeo
T
Hatakeyama
Masaharu
M
Sato
Yoshihiro
Y
Satoh
Kei
K
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000503:physiopathology; D007502:Iron Chelating Agents / Q000494:pharmacology; D008222:Lymphokines / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000893:Anti-Inflammatory Agents; D016228:Endothelial Growth Factors; D007502:Iron Chelating Agents; D008222:Lymphokines; D010972:Platelet Activating Factor; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003907:Dexamethasone; D003513:Cycloheximide; D003676:Deferoxamine