| Summary: | 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+, 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. Keywords:: ATP, endothelial cell, interferon-γ, P2X4 receptor, signal transducer and activator of transcription-1 (STAT1)
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