title: Triptolide inhibits proliferation of Epstein-Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1.
abstract: Epstein-Barr virus (EBV) infects various types of cells and mainly establishes latent infection in B lymphocytes. The viral latent membrane protein 1 (LMP1) plays important roles in transformation and proliferation of B lymphocytes infected with EBV. Triptolide is a compound of Tripterygium extracts, showing anti-inflammatory, immunosuppressive, and anti-cancer activities. In this study, it is determined whether triptolide inhibits proliferation of Epstein-Barr virus-positive B lymphocytes. The CCK-8 assays were performed to examine cell viabilities of EBV-positive B95-8 and P3HR-1 cells treated by triptolide. The mRNA and protein levels of LMP1 were examined by real time-PCR and Western blotting, respectively. The activities of two LMP1 promoters (ED-L1 and TR-L1) were determined by Dual luciferase reportor assay. The results showed that triptolide inhibited the cell viability of EBV-positive B lymphocytes, and the over-expression of LMP1 attenuated this inhibitory effect. Triptolide decreased the LMP1 expression and transcriptional levels in EBV-positive B cells. The activity of LMP1 promoter ED-L1 in type III latent infection was strongly suppressed by triptolide treatment. In addition, triptolide strongly reduced growth of B95-8 induced B lymphoma in BALB/c nude mice. These results suggest that triptolide decreases proliferation of EBV-induced B lymphocytes possibly by a mechanism related to down-regulation of the LMP1 expression.
authors.affiliation: Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, PR China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Pathology and Physiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, PR China.
authors.forename: Cong
authors.initials: C
authors.lastname: Long
authors.affiliation: Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, PR China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, PR China.
authors.forename: Jingchao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathogen Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, PR China; State Key Laboratory of Virology, Wuhan University, Wuhan 430072, PR China. Electronic address: xsun6@whu.edu.cn.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D015536:Down-Regulation; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010616:Phenanthrenes / Q000008:administration & dosage / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D004852:Epoxy Compounds; D010616:Phenanthrenes; D014763:Viral Matrix Proteins; C001899:triptolide
keywords: B lymphocytes; EBV; ED-L1; LMP1; Triptolide