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

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

来源：Nephrology Dialysis Transplantation, 2012, 27(1): 81-89.

DOI：10.1093/ndt/gfr271

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

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. %26lt;br%26gt;Methods. Conditionally immortalized human podocytes were evaluated for TLR expression. Based on high expression of TLR3, we evaluated the effect of polyinosinicpolycytidylic acid (polyIC), a TLR3 ligand, to induce CD80 expression in vitro. %26lt;br%26gt;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 %26lt; 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-kappa B) 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-kappa B. %26lt;br%26gt;Conclusions. Activation of TLR3 on cultured human podocytes induces CD80 expression and phenotypic change via an NF-kappa B-dependent mechanism and is partially blocked by dexamethasone. These studies provide a mechanism by which viral infections may cause proteinuria.

• 出版日期2012-1