title: Activation of Epstein-Barr virus by saliva from Sjogren's syndrome patients.
abstract: The aim of this study was to examine the mechanism of Epstein-Barr virus (EBV) activation by soluble factors from the inflamed salivary glands of patients with Sjogren's syndrome (SS). Saliva from SS patients was used to examine the regulation of EBV activation by an inflammatory salivary microenvironment. Transient transfection of the EBV-negative salivary gland cell line (HSY) with BZLF1, a trans-activating EBV gene promoter-fusion construct (Zp-luc), was used in this study. The results showed that under conditions where the BZLF1 promoter is activated by potent stimuli, SS saliva (from eight of 12 patients) exerts a significant effect on expression of the luciferase gene. A specific inhibitor of protein kinase C did not affect the SS saliva-induced Zp-luc activity, whereas treatment with inhibitors of calmodulin, calcineurin and IP3, dose-dependently decreased this induction. Transforming growth factor beta1 (TGF-beta1), which is known to be expressed in SS salivary glands, dose-dependently induced Zp-luc activity. Hence, these results demonstrate the activation of EBV by SS saliva and suggest that EBV activation at the inflammatory site may occur in the presence of TGF-beta1 via triggering of the mitogen-activated protein kinase (MAPK) kinase signalling pathway.
authors.affiliation: Department of Pathology, Tsurumi University School of Dental Medicine, Yokohama, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nagata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Inoue
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Higashiyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Mishima
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kizu
authors.forename: Ienaka
authors.initials: I
authors.lastname: Takeda
authors.forename: Fumio
authors.initials: F
authors.lastname: Mizuno
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Saito
mesh_terms: D000328:Adult; D001685:Biological Factors / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012463:Saliva / Q000821:virology*; D012469:Salivary Glands / Q000821:virology; D015398:Signal Transduction / Q000187:drug effects; D012859:Sjogren's Syndrome / Q000821:virology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014775:Virus Activation
chemical_list: C063676:BZLF1 protein, Herpesvirus 4, Human; D001685:Biological Factors; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C508960:TGFB1 protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014764:Viral Proteins; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases