title: Toll-like receptor 3 ligand, polyIC, induces proteinuria and glomerular CD80, and increases urinary CD80 in mice.
abstract: BACKGROUND
  We have reported that children with biopsy-proven minimal change disease (MCD) express CD80 (also known as B7.1) in their podocytes and excrete high levels of CD80 in their urine during active nephrotic syndrome. We also reported that polyIC, a Toll-like receptor 3 ligand, increases CD80 mRNA and protein expression in cultured human podocytes dose-dependently, with actin re-organization and a reduction in synaptopodin expression.
  
  
  METHODS
  To determine the effect of polyIC in the kidney, we subjected mice to systemic injection of polyIC or phosphate buffered saline.
  
  
  RESULTS
  Mice injected with polyIC developed significant proteinuria with increased urinary CD80 excretion. Glomeruli from mice injected with polyIC were normal by light microscopic examination, but showed increased CD80 production in podocytes by immunofluorescence staining. In isolated glomeruli from mice injected with polyIC, expressions of CD80 and interleukin 10 significantly increased with a mild non-significant increase in CTLA-4, and synaptopodin expression decreased significantly.
  
  
  CONCLUSIONS
  Our study demonstrates that systemically administered polyIC can induce transient proteinuria and urinary CD80 excretion with an increase in CD80 production in podocytes, increased glomerular CD80 and reduced synaptopodin expression. These findings may be relevant to the pathogenesis of proteinuria in MCD.
authors.affiliation: Division of Renal diseases and Hypertension, University of Colorado Denver, Aurora, CO, USA. Takuji.Ishimoto@ucdenver.edu
authors.forename: Takuji
authors.initials: T
authors.lastname: Ishimoto
authors.forename: Michiko
authors.initials: M
authors.lastname: Shimada
authors.forename: Garcia
authors.initials: G
authors.lastname: Gabriela
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosugi
authors.forename: Waichi
authors.initials: W
authors.lastname: Sato
authors.forename: Pui Y
authors.initials: PY
authors.lastname: Lee
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Lanaspa
authors.forename: Christopher
authors.initials: C
authors.lastname: Rivard
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Eduardo H
authors.initials: EH
authors.lastname: Garin
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007124:Immunoenzyme Techniques; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009402:Nephrosis, Lipoid; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011070:Poly I-C / Q000494:pharmacology*; D011507:Proteinuria / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D018122:B7-1 Antigen; D012333:RNA, Messenger; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D011070:Poly I-C