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|Title:||CD40 gene silencing reduces the progression of experimental lupus nephritis modulating local milieu and systemic mechanisms|
|Author:||Ripoll Llagostera, Èlia|
Aran Perramon, Josep M.
Ramon, Laura de
Herrero Fresneda, Immaculada
Bestard Matamoros, Oriol
Cruzado, Josep Ma.
Grinyó Boira, Josep M.
Torras Ambròs, Joan
|Keywords:||Malalties del ronyó|
|Publisher:||Public Library of Science (PLoS)|
|Abstract:||Lupus nephritis (LN) is an autoimmune disorder in which co-stimulatory signals have been involved. Here we tested a cholesterol-conjugated-anti-CD40-siRNA in dendritic cells (DC) in vitro and in a model of LPS to check its potency and tissue distribution. Then, we report the effects of Chol-siRNA in an experimental model of mice with established lupus nephritis. Our in vitro studies in DC show a 100%intracellular delivery of Chol-siRNA, with a significant reduction in CD40 after LPS stimuli. In vivo in ICR mice, the CD40-mRNA suppressive effects of our Chol-siRNA on renal tissue were remarkably sustained over a 5 days after a single preliminary dose of Chol-siRNA. The intra-peritoneal administration of Chol-siRNA to NZB/WF1 mice resulted in a reduction of anti-DNA antibody titers, and histopathological renal scores as compared to untreated animals. The higher dose of Chol-siRNA prevented the progression of proteinuria as effectively as cyclophosphamide, whereas the lower dose was as effective as CTLA4. Chol-siRNA markedly reduced insterstitialCD3+ and plasma cell infiltrates as well as glomerular deposits of IgG and C3. Circulating soluble CD40 and activated splenic lymphocyte subsets were also strikingly reduced by Chol-siRNA. Our data show the potency of our compound for the therapeutic use of anti-CD40-siRNA in human LN and other autoimmune disorders.|
|Note:||Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0065068|
|It is part of:||PLoS One, 2013, vol. 8, num. 6|
|Appears in Collections:||Articles publicats en revistes (Ciències Clíniques)|
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
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