Effects of interleukin-13 and montelukast on the expression of zonula occludens-1 in human podocytes

Yonsei Med J. 2015 Mar;56(2):426-32. doi: 10.3349/ymj.2015.56.2.426.

Abstract

Purpose: The aim of this study was to investigate whether pathologic changes in zonula occludens-1 (ZO-1) are induced by interleukin-13 (IL-13) in the experimental minimal-change nephrotic syndrome (MCNS) model and to determine whether montelukast, a leukotriene receptor antagonist, has an effect on ZO-1 restoration in cultured human podocytes.

Materials and methods: Human podocytes cultured on bovine serum albumin-coated plates were treated with different doses of IL-13 and montelukast and then examined for distribution using confocal microscopy and for ZO-1 protein levels using Western blotting.

Results: ZO-1 was internalized and shown to accumulate in the cytoplasm of human podocytes in an IL-13 dose-dependent manner. High doses (50 and 100 ng/mL) of IL-13 decreased the levels of ZO-1 protein at 12 and 24 h (both p<0.01; n=3), which were significantly reversed by a high dose (0.5 μM) montelukast treatment (p<0.01; n=3).

Conclusion: Our results suggest that IL-13 alters the expression of ZO-1, and such alterations in the content and distribution of ZO-1 may be relevant in the pathogenesis of proteinuria in the MCNS model.

Keywords: Interleukin-13; leukotriene receptor antagonists; podocytes; zonula occludens-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / pharmacology*
  • Blotting, Western
  • Cyclopropanes
  • Dose-Response Relationship, Drug
  • Humans
  • Interleukin-13 / pharmacology*
  • Leukotriene Antagonists / pharmacology*
  • Microscopy, Confocal
  • Podocytes / drug effects*
  • Podocytes / metabolism
  • Proteinuria / pathology
  • Quinolines / pharmacology*
  • Sulfides
  • Tight Junctions
  • Zonula Occludens-1 Protein / metabolism*

Substances

  • Acetates
  • Cyclopropanes
  • Interleukin-13
  • Leukotriene Antagonists
  • Quinolines
  • Sulfides
  • Zonula Occludens-1 Protein
  • montelukast