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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/69387
CD40 gene silencing reduces the progression of experimental lupus nephritis modulating local milieu and systemic mechanisms
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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.
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RIPOLL LLAGOSTERA, Èlia, MERINO, Ana, GOMÀ, Montse, ARAN PERRAMON, Josep m., BOLAÑOS, Núria, RAMON, Laura de, HERRERO FRESNEDA, Immaculada, BESTARD MATAMOROS, Oriol, CRUZADO, Josep ma., GRINYÓ BOIRA, Josep m., TORRAS AMBRÒS, Joan. CD40 gene silencing reduces the progression of experimental lupus nephritis modulating local milieu and systemic mechanisms. _PLoS One_. 2013. Vol. 8, núm. 6. [consulta: 23 de gener de 2026]. ISSN: 1932-6203. [Disponible a: https://hdl.handle.net/2445/69387]