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

Nephrol Dial Transplant. 2012 Jan;27(1):81-9. doi: 10.1093/ndt/gfr271. Epub 2011 May 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • B7-1 Antigen / antagonists & inhibitors
  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism*
  • Blotting, Western
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism*
  • Dexamethasone / pharmacology
  • Fluorescent Antibody Technique
  • Humans
  • Lipopolysaccharides / pharmacology
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Podocytes / cytology
  • Podocytes / drug effects
  • Podocytes / metabolism*
  • Poly I-C / pharmacology
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / metabolism*


  • Anti-Inflammatory Agents
  • B7-1 Antigen
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • RNA, Small Interfering
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Dexamethasone
  • Poly I-C