Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/69387
Title: CD40 gene silencing reduces the progression of experimental lupus nephritis modulating local milieu and systemic mechanisms
Author: Ripoll Llagostera, Èlia
Merino, Ana
Gomà, Montse
Aran Perramon, Josep M.
Bolaños, Nuria
Ramon, Laura de
Herrero Fresneda, Immaculada
Bestard Matamoros, Oriol
Cruzado, Josep Ma.
Grinyo Boira, Josep M.
Torras Ambròs, Joan
Keywords: Malalties del ronyó
RNA
Kidney diseases
RNA
Issue Date: 14-Jun-2013
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
Related resource: http://dx.doi.org/10.1371/journal.pone.0065068
URI: http://hdl.handle.net/2445/69387
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Files in This Item:
File Description SizeFormat 
652722.pdf1.74 MBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons