title: Interferon (IFN)-Induced Protein 35 (IFI35), a Type I Interferon-Dependent Transcript, Upregulates Inflammatory Signaling Pathways by Activating Toll-Like Receptor 3 in Human Mesangial Cells.
abstract: OBJECTIVE
  Activation of Toll-like receptor 3 (TLR3) signaling followed by type I interferon (IFN) expression is crucial in antiviral and "pseudoviral" immune reactions in renal mesangial cells (MCs). These reactions are probably involved in the pathogenesis of chronic kidney disease (CKD). However, the role of IFN-induced 35-kDa protein 35 (IFI35), a type I IFN-dependent transcript, in glomerular inflammation is unclear. Here, we aimed to investigate the expression and the role of IFI35 in IFN-β/retinoic acid-inducible gene-I (RIG-I)/CCL5 and IFN-β/melanoma differentiation-associated gene 5 (MDA5)/CXCL10 axes in MCs.
  
  
  METHODS
  We treated human MCs with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, then analysed the IFI35 expression by reverse transcription-polymerase chain reaction and western blotting. To examine the regulation of IFI35 expression, we subjected MCs to RNA interference (siRNA) against IFN-β, RIG-I, and MDA5.
  
  
  RESULTS
  Activation of TLR3 by poly IC induces the IFI35 expression in MCs. siRNA against IFN-β inhibited poly IC-induced IFI35 expression. Knockdown of IFI35 resulted in a decrease of poly IC-induced RIG-I and MDA5 protein as well as decreased CCL5 and CXCL10 mRNA and protein expression. However, it did not affect the expression of none of phosphorylated signal transducers or activator of transcription (STAT) 1 protein, or RIG-I and MDA5 in mRNA levels.
  
  
  CONCLUSIONS
  Regional expression of IFI35 and its dysregulation may be involved in the pathogenesis of glomerular inflammation in CKD.
authors.affiliation: Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Chikashi
authors.initials: C
authors.lastname: Yano
authors.forename: Akiko
authors.initials: A
authors.lastname: Numata
authors.forename: Koji
authors.initials: K
authors.lastname: Tsugawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Hayakari
authors.forename: Tomoh
authors.initials: T
authors.lastname: Matsumiya
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Shojiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kazushi
authors.initials: K
authors.lastname: Tsuruga
authors.forename: Shogo
authors.initials: S
authors.lastname: Kawaguchi
authors.forename: Manabu
authors.initials: M
authors.lastname: Murakami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D007370:Interferon Type I / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D007678:Kidney Glomerulus / Q000473:pathology; D050527:Mesangial Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000209:etiology; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C085378:IFI35 protein, human; D007370:Interferon Type I; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3