Toll-like receptor 3 ligands induce CD80 expression in human podocytes via an NF-κB-dependent pathway

Michiko Shimada*, Takuji Ishimoto, Pui Y. Lee, Miguel A. Lanaspa, Christopher J. Rivard, Carlos A. Roncal-Jimenez, David T. Wymer, Hideaki Yamabe, Peter W. Mathieson, Moin A. Saleem, Eduardo H. Garin, Richard J. Johnson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Background.Recent studies suggest that CD80 (also known as B7.1) is expressed on podocytes in minimal-change disease (MCD) and may have a role in mediating proteinuria. CD80 expression is known to be induced by Toll-like receptor (TLR) ligands in dendritic cells. We therefore evaluated the ability of TLR to induce CD80 in human cultured podocytes. Methods.Conditionally immortalized human podocytes were evaluated for TLR expression. Based on high expression of TLR3, we evaluated the effect of polyinosinic-polycytidylic acid (polyIC), a TLR3 ligand, to induce CD80 expression in vitro. Results.TLR1-6 and 9 messenger RNA (mRNA) were expressed in podocytes. Among TLR ligands 1-9, CD80 mRNA expression was significantly induced by polyIC and lipopolysaccharide (TLR4 ligand) with the greatest stimulation by polyIC (6.8 ± 0.7 times at 6 h, P < 0.001 versus control). PolyIC induced increased expression of Cathepsin L, decreased synaptopodin expression and resulted in actin reorganization which suggested a similar injury pattern as observed with lipopolyssaccharide. PolyIC induced type I and type II interferon signaling, nuclear factor kappa B (NF-κB) activation and the induction of CD80 expression. Knockdown of CD80 protected against actin reorganization and reduced synaptopodin expression in response to polyIC. Dexamethasone, a corticosteroid commonly used to treat MCD, also blocked both basal and polyIC-stimulated CD80 expression, as did inhibition of NF-κB. Conclusions.Activation of TLR3 on cultured human podocytes induces CD80 expression and phenotypic change via an NF-κB-dependent mechanism and is partially blocked by dexamethasone. These studies provide a mechanism by which viral infections may cause proteinuria.

Original languageEnglish (US)
Pages (from-to)81-89
Number of pages9
JournalNephrology Dialysis Transplantation
Volume27
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • CD80
  • Toll-like receptor
  • corticosteroids
  • minimal-change disease

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Fingerprint Dive into the research topics of 'Toll-like receptor 3 ligands induce CD80 expression in human podocytes via an NF-κB-dependent pathway'. Together they form a unique fingerprint.

Cite this