Selective Up-regulation of P2X_4-Receptor Gene Expression by Interferon-γ in Vascular Endothelial Cells
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概要
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Extracellular nucleotides are involved in the development of vascular inflammation. However, little is known about whether effects of nucleotides are modulated under inflammatory states. We investigated effects of interferon-γ (INF-γ) on ATP-induced responses in vascular endothelial cells. Treatment of human umbilical vein endothelial cells (HUVECs) with IFN-γ for 24 h resulted in an enhancement of the ATP-induced increase in intracellular Ca2+ concentration ([Ca2+]i) without affecting the UTP-induced one. The increased Ca2+ response to ATP in IFN-γ–treated cells was dependent on the extracellular Ca2+, and was not inhibited by the phospholipase C inhibitor U73122. RT-PCR and Western blotting revealed that HUVECs dominantly expressed P2X4 receptor. IFN-γ increased P2X4-receptor mRNA and protein, accompanied by an increase in ATP-triggered membrane current. IFN-γ did not affect P2X4-receptor mRNA stability, but increased P2X4-receptor gene transcription in a cycloheximide-insensitive manner. IFN-γ stimulated phosphorylation of signal transducer and activator of transcription-1 (STAT1). Epigallocatechin gallate (EGCG), an inhibitor of STAT1-mediated signaling, and AG490, a Janus kinase (JAK) inhibitor, impaired P2X4-receptor mRNA up-regulation by IFN-γ. These results indicate that INF-γ selectively increases P2X4-receptor gene expression, leading to an up-regulation of purinergic signaling in vascular endothelial cells.
- 社団法人 日本薬理学会の論文
- 2008-08-20
著者
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Kimura Junko
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University
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Ono Tomoyuki
Department of Pharmacology, School of Medicine, Fukushima Medical University, Japan
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Kimura J
Dep. Of Pharmacology School Of Medicine Fukushima Medical Univ. Jpn
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INOUE Kazuhide
Department of Pharmacy, Fukuoka University Hospital
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Kimura J
Department Of Pharmacology Fukushima Medical University School Of Medicine
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Ono Tomoyuki
Department Of Pharmacology Fukushima Medical University School Of Medicine
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Ono Tomoyuki
Department Of Pharmacology Fukushima Medical College
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MATSUOKA Isao
Department of Pharmacology, Fukushima Medical University, School of Medicine
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Matsuoka Isao
Department Of Pharmacology Fukushima Medical College
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Inoue Kazuhide
Department Of Pharmacology Graduate School Of Pharmaceutical Science Kyushu University
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TANG Yan
Department of Pharmacology, Fukushima Medical University School of Medicine
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Tang Yan
Department Of Histology And Embryology Peking University Health Science Center
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Tang Yan
Department Of Pharmacology Fukushima Medical University School Of Medicine
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Matsuoka Isao
Department Of Anesthesiology Ilikai Medical Inc Kakizoe Hospital
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Matsuoka Isao
Dep. Of Pharmacology Fukushima Medical Univ. School Of Medicine Jpn
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Inoue Kazuhide
Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University
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