title: Interleukin-4 and interleukin-13 act on glomerular visceral epithelial cells.
abstract: In minimal change nephrosis (MCN), proteinuria is associated with structural changes of the glomerular visceral epithelial cells (GVEC). The occurrence of MCN has been associated with 2 lymphocyte-dependent conditions. To examine a direct role for type 2 cytokines in GVEC injury, the expression of interleukin (IL)-4/IL-13 receptors by GVEC and direct effects of IL-4 and IL-13 on GVEC were studied. Reverse transcription-PCR showed that isolated human and rat glomeruli and cultured human and rat GVEC expressed mRNA for IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2. Protein expression of [L-4Ralpha and IL-13Ralpha2 by GVEC in human kidney biopsies and by cultured human GVEC was detected by immunohistochemistry. Western blotting demonstrated phosphorylation of STAT6 in cultured GVEC upon incubation with IL-4 or IL-13. This indicated signal transduction via the heterodimeric receptor complex IL-4R2, which is composed of the IL-4Ralpha and the IL-13Ralpha1. Direct effects on GVEC function were examined in monolayer experiments. IL-4 and IL-13 dose-dependently decreased transepithelial electrical resistance of monolayers of rat GVEC to approximately 30 and 40% of baseline values, respectively. The transepithelial electrical resistance decrease was associated with a significant increase in short-circuit current, whereas no changes were observed in the transmonolayer flux of the macromolecules horseradish peroxidase (molecular weight, 44 kD) and 14C-mannitol (molecular weight, 182 Da). No changes in cell structure were observed with electron microscopy. It is concluded that by binding to specific IL-4/ IL-13 receptors, IL-4 and IL-13 can exert specific effects on GVEC function, which could be of pathogenetic relevance for glomerular injury in MCN.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: José G
authors.initials: JG
authors.lastname: VAN DEN Berg
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Aten
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M Anwar
authors.initials: MA
authors.lastname: Chand
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Nike
authors.initials: N
authors.lastname: Claessen
authors.affiliation: Department of Cell Physiology, University of Nijmegen, The Netherlands.
authors.forename: Lisette
authors.initials: L
authors.lastname: Dijkink
authors.affiliation: Diaclone, Besançon, France.
authors.forename: John
authors.initials: J
authors.lastname: Wijdenes
authors.affiliation: Renal Division, Emory University School of Medicine and Veterans Affair Medical Center, Atlanta, Georgia.
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Lakkis
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Weening
mesh_terms: D000818:Animals; D002460:Cell Line; D004553:Electric Conductivity; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D046911:Macromolecular Substances; D010539:Permeability; D010766:Phosphorylation; D051381:Rats; D018123:Receptors, Interleukin / Q000378:metabolism; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
chemical_list: C508181:IL13RA1 protein, human; C508185:Il13ra1 protein, rat; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D046911:Macromolecular Substances; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D015847:Interleukin-4; D007770:L-Lactate Dehydrogenase