title: Retinoic acid-inducible gene-I is induced by double-stranded RNA and regulates the expression of CC chemokine ligand (CCL) 5 in human mesangial cells.
abstract: BACKGROUND
  Retinoic acid-inducible gene-I (RIG-I) is a putative RNA helicase involved in immune reactions against RNA viruses and various inflammatory and autoimmune diseases. The purpose of the present study was to investigate the role of RIG-I in glomerular diseases.
  
  
  METHODS
  We treated human mesangial cells in culture with polyinosinic-polycytidylic acid (poly IC), which is an authentic double-stranded RNA, and analysed the expression of RIG-I, CC chemokine ligand 5 (CCL5) and interferon (IFN)-β by western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) or enzyme-linked immunosorbent assay (ELISA). To elucidate the poly IC-signalling pathway, we subjected the cells to RNA interference (RNAi) against RIG-I, IFN-β or Toll-like receptor (TLR) 3. Furthermore, we studied the effects of IFN-β receptor blocking and IFN-β overexpression.
  
  
  RESULTS
  Poly IC induced the expression of RIG-I and CCL5 in human mesangial cells, and RNAi against RIG-I inhibited this poly IC-induced CCL5 expression. Poly IC-induced RIG-I expression was also inhibited by RNAi against IFN-β and by an antibody against the IFN-β receptor. IFN-β overexpression induced the expression of both RIG-I and CCL5. The knockdown of TLR3 abolished poly IC-induced RIG-I expression.
  
  
  CONCLUSIONS
  The TLR3/IFN-β/RIG-I/CCL5 signalling pathway may mediate immune and inflammatory responses against viral infection in mesangial cells, suggesting the role of this pathway in the aggravation of glomerulonephritis due to viral infection.
authors.affiliation: Department Vascular Biology, Hirosaki University Graduate School of Medicine, Zaifu-cho, Hirosaki, Japan.
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Tomoh
authors.initials: T
authors.lastname: Matsumiya
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.forename: Kazushi
authors.initials: K
authors.lastname: Tsuruga
authors.forename: Eishin
authors.initials: E
authors.lastname: Oki
authors.forename: Tomomi
authors.initials: T
authors.lastname: Aizawa-Yashiro
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
authors.forename: Kei
authors.initials: K
authors.lastname: Satoh
mesh_terms: D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D016899:Interferon-beta / Q000502:physiology; D050527:Mesangial Cells / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D011971:Receptors, Immunologic; D051196:Toll-Like Receptor 3 / Q000502:physiology
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D003907:Dexamethasone; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D011070:Poly I-C