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J Am Soc Nephrol 11:413-422, 2000
© 2000 American Society of Nephrology

Interleukin-4 and Interleukin- 13 Act on Glomerular Visceral Epithelial Cells

JOSÉ G. VAN DEN BERG*, JAN ATEN*, M. ANWAR CHAND*, NIKE CLAESSEN*, LISETTE DIJKINK{dagger}, JOHN WIJDENES{ddagger}, FADI G. LAKKIS§ and JAN J. WEENING*

* Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
{dagger} Department of Cell Physiology, University of Nijmegen, The Netherlands
{ddagger} Diaclone, Besançon, France
§ Renal Division, Emory University School of Medicine and Veterans Affair Medical Center, Atlanta, Georgia.

Correspondence to Dr. José G. van den Berg, Department of Pathology, L2-256, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Phone: +31 20 566 4935; Fax: +31 20 696 0389; E-mail: j.g.vandenberg{at}amc.uva.nl

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 T-helper2 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-4R{alpha}, IL-13R{alpha}1, and IL-13R{alpha}2. Protein expression of IL-4R{alpha} and IL-13R{alpha}2 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-4R{alpha} and the IL-13R{alpha}1. 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.




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