title: Polyinosinic-polycytidylic acid induces the expression of interferon-stimulated gene 20 in mesangial cells.
abstract: OBJECTIVE
  Interferon (IFN)-stimulated gene 20 (ISG20) is a 3'-to-5' exonuclease specific for single-stranded RNA and involved in host defense reactions against RNA viruses. The expression and the role of ISG20 in mesangial cells have not been reported.
  
  
  METHODS
  Normal human mesangial cells were cultured and treated with polyinosinic-polycytidylic acid (poly (I:C)), an authentic double-stranded RNA which mimics viral infection to cells. The effect of RNA interference of Toll-like receptor 3 (TLR3) or IFN-β on the ISG20 expression was examined. The effect of a blocking antibody against the receptor for IFN-β or anti-inflammatory steroid dexamethasone was also examined.
  
  
  RESULTS
  Treatment of cells with poly (I:C) induced the expression of ISG20. The poly (I:C)-induced expression of ISG20 was inhibited by knockdown of TLR3, IFN regulatery factor 3 (IRF3) or IFN-β. Blocking of the receptor for IFN-β suppressed and overexpression of IFN-β enhanced ISG20 expression. The poly (I:C)-induced expressions of IFN-β and ISG20 were inhibited by dexamethasone. Transfection of mesangial cells with poly (I:C) or 5'-triphosphate single-stranded RNA as a complex with cationic lipid also induced the expression of ISG20, and this was inhibited by knockdown of retinoic acid-inducible gene-I (RIG-I).
  
  
  CONCLUSIONS
  Poly (I:C) induces the expression of ISG20 in mesangial cells. ISG20 may be involved in anti-viral reactions in renal mesangial cells. TLR3, IRF3 and de novo synthesized IFN-β may mediate the poly (I:C)-induced expression of ISG20, and RIG-I may mediate ISG20 expression induced by poly (I:C)/cationic lipid complex.
authors.affiliation: Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. timaizum@cc.hirosaki-u.ac.jp
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Nadir
authors.initials: N
authors.lastname: Mechti
authors.forename: Tomoh
authors.initials: T
authors.lastname: Matsumiya
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Sato
authors.forename: Tomomi
authors.initials: T
authors.lastname: Aizawa-Yashiro
authors.forename: Kazushi
authors.initials: K
authors.lastname: Tsuruga
authors.forename: Ryo
authors.initials: R
authors.lastname: Hayakari
authors.forename: Kei
authors.initials: K
authors.lastname: Satoh
mesh_terms: D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D005092:Exonucleases / Q000096:biosynthesis*; D005095:Exoribonucleases; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology*; D034622:RNA Interference; D011971:Receptors, Immunologic; D051196:Toll-Like Receptor 3 / Q000235:genetics
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D011971:Receptors, Immunologic; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D003907:Dexamethasone; D005092:Exonucleases; D005095:Exoribonucleases; C112346:ISG20 protein, human; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D011070:Poly I-C