title: Glomerular expression of fractalkine is induced by polyinosinic-polycytidylic acid in human mesangial cells: possible involvement of fractalkine after viral infection.
abstract: BACKGROUND
  Viral infections often trigger the onset or worsening of glomerular diseases, but the details of this mechanism are unclear. Fractalkine/CX3CL1 (Fkn) is a chemokine that induces the chemotaxis and activation of cells expressing its receptor, CX3CR1. To examine the involvement of glomerular Fkn expression in the development of glomerulonephritis after viral infection, we conducted experimental studies using human mesangial cells (MCs) in culture.
  
  
  METHODS
  We examined the effect of polyinosinic-polycytidylic acid (poly IC), an authentic viral double-stranded RNA, on Fkn expression in MCs to investigate the involvement of Fkn in the antiviral reaction of MCs. Fkn mRNA and protein were analyzed using real-time PCR and enzyme-linked immunosorbent assay. Also, an immunofluorescent study to examine mesangial Fkn expression in biopsy specimens obtained from patients with glomerulonephritis was conducted.
  
  
  RESULTS
  Poly IC-induced Fkn expression in MCs in both a time- and dose-dependent manner, and RNA interference (RNAi) against Toll-like receptor 3 (TLR3) or interferon regulatory factor 3 (IRF3) inhibited poly IC-induced Fkn expression. Significant glomerular Fkn expression was observed in biopsy specimens from patients with immunoglobulin A nephropathy and purpura nephritis, with increasing severity of glomerular inflammation.
  
  
  CONCLUSIONS
  The TLR3/IRF3/Fkn signaling pathway may, at least in part, mediate immune and inflammatory responses against viral infection in MCs.
authors.affiliation: Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Aizawa-Yashiro
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Kazushi
authors.initials: K
authors.lastname: Tsuruga
authors.forename: Shojiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Tomoh
authors.initials: T
authors.lastname: Matsumiya
authors.forename: Ryo
authors.initials: R
authors.lastname: Hayakari
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Kei
authors.initials: K
authors.lastname: Satoh
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000821:virology; D011070:Poly I-C / Q000494:pharmacology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D055815:Young Adult
chemical_list: C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D012333:RNA, Messenger; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D011070:Poly I-C