國家衛生研究院 NHRI:Item 3990099045/2079

NHRI > National Institute of Infectious Diseases and Vaccinology > Ih-Jen Su(2002-2015) > Periodical Articles > Item 3990099045/2079

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Title:	Epstein-Barr virus (EBV) latent membrane protein-1 down-regulates tumor necrosis factor-alpha (TNF-alpha) receptor-1 and confers resistance to TNF-alpha-induced apoptosis in T cells - Implication for the progression to T-cell lymphoma in EBV-associated hemophagocytic syndrome
Other Titles:	Epstein-Barr virus (EBV) latent membrane protein-1 down-regulates tumor necrosis factor-α (TNF-α) receptor-1 and confers resistance to TNF-α-induced apoptosis in T cells: implication for the progression to T-cell lymphoma in EBV-associated hemophagocytic syndrome
Authors:	Chuang, HC;Lay, JD;Chuang, SE;Hsieh, WC;Chang, Y;Su, IJ
Contributors:	Division of Clinical Research;National Institute of Cancer Research
Abstract:	The infection of T cells by Epstein-Barr virus (EBV) may result in hemophagocytic syndrome (HPS) through enhanced cytokine secretion, particularly tumor necrosis factor-alpha (TNF-alpha), by EBV latent membrane protein-1 (LMP-1). One bewildering observation of HPS patients is relapsing disease or progression to T-cell lymphoma. This finding raises the question whether EBV LMP-1-expressing T cells may survive and proliferate in the cytokine milieu of HPS. To explore this possibility, we tested the sensitivity of LMP-1-expressing T cells to apoptosis in the presence of TNF-a. LMP-1 up-regulated TNF-alpha through TRAF2,5 and nuclear factor-kappa B pathway in T cells. The LMP-1-expressing T cells then became resistant to TN17-a-induced apoptosis. Interestingly, the expression of TNFR1 was remarkably down-regulated by LMP-1 in T cells. Furthermore, the TNF-alpha/TNFR1 downstream death signal TNFR1-associated death domain protein was constitutively recruited by LMP-1, and the activities of apoptotic caspases 3, 8, and 9 were suppressed. Reconstitution of TNFR1 successfully reversed the TNF-alpha-induced apoptotic cascades. Therefore, EBV LMP-1 not only activates T cells to proliferate but also confers resistance to TNF-alpha-mediated apoptosis via down-regulation of TNFR1 in the cytokine milieu of HPS. This finding provides a potential mechanism to explain the disease persistence or progression T-cell lymphoma HPS patients.
Keywords:	Pathology
Date:	2007-05
Relation:	American Journal of Pathology. 2007 May;170(5):1607-1617.
Link to:	http://dx.doi.org/10.2353/ajpath.2007.061026
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:000246050400017
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=34250838092
Appears in Collections:	[Ih-Jen Su(2002-2015)] Periodical Articles [Yao Chang] Periodical Articles [Shuang-En Chuang] Periodical Articles [Huai-Chia Chuang] Periodical Articles

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