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- Title
Toll-like receptor 3 ligand, polyIC, induces proteinuria and glomerular CD80, and increases urinary CD80 in mice.
- Authors
Ishimoto, Takuji; Shimada, Michiko; Gabriela, Garcia; Kosugi, Tomoki; Sato, Waichi; Lee, Pui Y.; Lanaspa, Miguel A.; Rivard, Christopher; Maruyama, Shoichi; Garin, Eduardo H.; Johnson, Richard J.
- Abstract
Background We have reported that children with biopsy-proven minimal change disease (MCD) express CD80 (also known as B7.1) in their podocytes and excrete high levels of CD80 in their urine during active nephrotic syndrome. We also reported that polyIC, a Toll-like receptor 3 ligand, increases CD80 mRNA and protein expression in cultured human podocytes dose-dependently, with actin re-organization and a reduction in synaptopodin expression. Methods To determine the effect of polyIC in the kidney, we subjected mice to systemic injection of polyIC or phosphate buffered saline. Results Mice injected with polyIC developed significant proteinuria with increased urinary CD80 excretion. Glomeruli from mice injected with polyIC were normal by light microscopic examination, but showed increased CD80 production in podocytes by immunofluorescence staining. In isolated glomeruli from mice injected with polyIC, expressions of CD80 and interleukin 10 significantly increased with a mild non-significant increase in CTLA-4, and synaptopodin expression decreased significantly. Conclusions Our study demonstrates that systemically administered polyIC can induce transient proteinuria and urinary CD80 excretion with an increase in CD80 production in podocytes, increased glomerular CD80 and reduced synaptopodin expression. These findings may be relevant to the pathogenesis of proteinuria in MCD.
- Subjects
TOLL-like receptors; PROTEINURIA; GLOMERULAR filtration rate; CD80 antigen; GENE expression; IMMUNOFLUORESCENCE; LABORATORY mice
- Publication
Nephrology Dialysis Transplantation, 2013, Vol 28, Issue 6, p1439
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfs543