Double-stranded RNA activates type I interferon secretion in glomerular endothelial cells via retinoic acid-inducible gene (RIG)-1

Nephrol Dial Transplant. 2009 Nov;24(11):3312-8. doi: 10.1093/ndt/gfp339. Epub 2009 Jul 16.


Background: The molecular pathomechanisms by which viral infections trigger glomerulonephritis remain elusive. In the glomerulus, glomerular endothelial cells (GEnC) first interact with circulating viral particles; hence, we hypothesized that viral RNA, a known inducer of type I interferons and cytokines in dendritic cells, would also elicit proinflammatory antiviral reponses in GEnC.

Methods: Cultured murine GEnC were stimulated with poly I:C RNA and phenotype changes were assessed. Specific antagonists or s.i.RNA were used to determine the mechanisms of RNA uptake and the functional role of putative RNA receptors.

Results: Poly I:C RNA activated GEnC to produce IL-6, CCL2, CCL5, CXCL10, IFN-alpha and IFN-beta. This was independent of endosomal acidification or MyD88 but required complex formation with cationic lipids to be taken up into GEnC via clathrin-dependent endocytosis. RIG-1- but not MDA5-specific s.i.RNA prevented GEnC activation. Type I interferon production did not activate GEnC in an autocrine-paracrine manner. Complexed RNA also activated GEnC to express ICAM-1 and increased the albumin permeability of GEnC monolayers.

Conclusions: Complexed dsRNA enters GEnC via clathrin endocytosis and activates GEnC via RIG-1 in the cytosol to produce inflammatory cytokines, chemokines and type I interferons. Furthermore, RNA induces ICAM-1 expression and increases GEnC permeability. All of these mechanisms may contribute to the onset or aggravation of glomerulonephritis associated with RNA virus infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / metabolism
  • Animals
  • Cells, Cultured
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / physiology*
  • Endocytosis
  • Endothelial Cells / immunology*
  • Glomerulonephritis / etiology*
  • Intercellular Adhesion Molecule-1 / analysis
  • Interferon Type I / biosynthesis*
  • Interferon-Induced Helicase, IFIH1
  • Kidney Glomerulus / immunology*
  • Mice
  • Poly I-C / pharmacology
  • RNA Virus Infections / complications*
  • RNA, Double-Stranded / physiology*
  • Toll-Like Receptors / physiology
  • Vascular Cell Adhesion Molecule-1 / analysis


  • Albumins
  • Interferon Type I
  • RNA, Double-Stranded
  • Toll-Like Receptors
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Ddx58 protein, mouse
  • Ifih1 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1
  • Poly I-C