title: Novel expression and regulation of TIMP-1 in Epstein Barr virus-infected cells and its impact on cell survival.
abstract: Epstein Barr virus (EBV) uses various strategies to manipulate host cytokine production in favor of the survival of infected B-cells. Microarray and cytokine protein array assays revealed that tissue inhibitor of metalloproteinase-1 (TIMP-1) was significantly up-regulated in EBV-infected primary B cells and maintained in abundance in EBV-immortalized lymphoblastoid cell lines (LCLs). TIMP-1 plays critical roles in extracellular matrix homeostasis and regulates signaling pathways. In this study, we demonstrated that the EBV-encoded immediate early lytic protein, Zta, upregulates mainly TIMP-1 expression by binding to the AP-1 site within the TIMP-1 promoter. Moreover, knockdown of TIMP-1 expression promoted cisplastin and cold shock-induced death of LCLs. This study provides a mechanistic link between EBV-induced TIMP-1 expression and its impact on LCL survival.
authors.affiliation: Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Graduate institute of Medical Biotechnology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Sue-Jane
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Wu
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Chou
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Jiun-Han
authors.initials: JH
authors.lastname: Lin
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ya-Chi
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Mei-Ru
authors.initials: MR
authors.lastname: Chen
authors.affiliation: Institute of Systems Biology and Bioinformatics, National Central University, Room 204, No.300, Jhongda Road, Jhongli, Taoyuan County 32001, Taiwan. Electronic address: nianhan.ma@gmail.com.
authors.forename: Nianhan
authors.initials: N
authors.lastname: Ma
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: chtsai@ntu.edu.tw.
authors.forename: Ching-Hwa
authors.initials: CH
authors.lastname: Tsai
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D002470:Cell Survival; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D015534:Trans-Activators; D018808:Transcription Factor AP-1
keywords: Apoptosis; EBV; LCL; TIMP-1; Zta