國家衛生研究院 NHRI:Item 3990099045/3325

NHRI > National Institute of Infectious Diseases and Vaccinology > Ih-Jen Su(2002-2015) > Periodical Articles > Item 3990099045/3325

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Title:	Up-regulation of activating transcription factor-5 suppresses SAP expression to activate T cells in hemophagocytic syndrome associated with Epstein-Barr virus infection and immune disorders
Authors:	Chuang, HC;Wang, JM;Hsieh, WC;Chang, Y;Su, IJ
Contributors:	Division of Clinical Research
Abstract:	Hemophagocytic syndrome (HPS) is a fatal, pro-inflammatory cytokine disorder that is associated with viral infections and immune disorders. Previously, we demonstrated that Epstein-Barr virus latent membrane protein-1 (LMP-1) could down-regulate the SAP gene, enhancing Th1 cytokine secretion in T cells and leading to HPS. The exact mechanism of SAP gene regulation by LMP-1 remains to be clarified. In this study, using cDNA microarray analysis, we identified ATF5 as the candidate transcriptional repressor for SAP expression in LMP-1-expressing T cells. LMP-1 up-regulated ATF5 via TRAF2,5/NF-?B signals to suppress SAP gene expression. Reporter assays and electrophoretic mobility shift assays revealed that ATF5 bound differentially to two sites of the SAP promoter. In resting T cells, ATF5 bound predominantly to the high-affinity site in the -81 to -74 region while additionally binding to the low-affinity site at -305 to -296 in LMP-1-expressing T cells. Such binding subsequently disrupted the transcription of the SAP gene. At the same time, Th1 cytokine secretion was enhanced. This phenomenon was also observed in conditions such as ATF5 overexpression, phytohemagglutinin stimulation of primary T cells, and ligand engagement of T-cell lines. Therefore, the down-regulation of the SAP gene by ATF5 may represent a common mechanism for the pathogenesis of HPS that is associated with either Epstein-Barr virus infection or immune disorders with dysregulated T-cell activation.
Date:	2008-11
Relation:	American Journal of Pathology. 2008 Nov;173(5):1397-1405.
Link to:	http://dx.doi.org/10.2353/ajpath.2008.080440
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0002-9440&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000260726400015
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=55349096161
Appears in Collections:	[Ih-Jen Su(2002-2015)] Periodical Articles [Yao Chang] Periodical Articles [Huai-Chia Chuang] Periodical Articles

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