title: Predominant contribution of IFN-beta expression to apoptosis induction in human uterine cervical fibroblast cells by influenza-virus infection.
abstract: We have been investigating an apoptosis induction in human fetal membrane cells by influenza virus (IV) infection and the contribution of apoptosis induction to the viral infection-defense response between a fetus and the maternal body. For studying any role of uterine cells in the anti-viral response, we investigated the molecular mechanism of the apoptotic induction in human uterine cervical fibroblast cell line (HCF) by IV infection. IV type A and B infection induced DNA fragmentation in HCF. In IV-infected HCF, gene mRNA expression levels of interleukine (IL)-1beta, IL-6, tumor necrosis factor (TNF) alpha, Fas ligand, interferon regulatory factor (IRF)-1, interferon (IFN) alpha and IFN beta increased as compared with those in mock treatment cells, and the induction of mRNAs for double stranded RNA dependent protein kinase (PKR), indolamine 2,3-deoxygenase (IDO) and 2'-5' oligoadenylate synthetase (2-5 OAS) were indicated, which had a role for a host defense response induced by IFN-beta. The amount of IFN-beta protein increased by IV-infection, and DNA fragmentation was inhibited with anti-IFN-beta antibody and PKR inhibitor (2-aminopurine). Furthermore, a synthetic double stranded RNA, poly I : C, could induce almost the same phenomena as that induced by virus infection. We conclude that IV-infection induces the apoptosis in HCF cells through the IFN-beta expression regulated by double stranded RNA and IRF-1 induction, and suggest that the IFN-beta induction may be the predominant contribution to the IV infection induced HCF apoptosis.
authors.affiliation: Department of Clinical Molecular Genetics, Faculty of Pharmacy, Tokyo University of Pharmacy & Life Science, Hachioji, Tokyo, Japan. ohyamak@ps.toyaku.ac.jp
authors.forename: Kunio
authors.initials: K
authors.lastname: Ohyama
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sano
authors.forename: Hiroo
authors.initials: H
authors.lastname: Toyoda
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000378:metabolism* / Q000821:virology; D053938:DNA Fragmentation; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007251:Influenza, Human / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D029521:Alphainfluenzavirus; D029524:Betainfluenzavirus; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D011070:Poly I-C / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D016899:Interferon-beta; D011070:Poly I-C