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dc.contributor.authorGorina, Roser-
dc.contributor.authorSantalucía, Tomàs-
dc.contributor.authorPetegnief, Valérie-
dc.contributor.authorEjarque-Ortiz, Aroa-
dc.contributor.authorSaura, Josep-
dc.contributor.authorPlanas, Anna M.-
dc.date.accessioned2011-04-29T12:27:14Z-
dc.date.available2011-04-29T12:27:14Z-
dc.date.issued2009-01-01-
dc.identifier.citationGlia (57)1: 93-107 (2009)es_ES
dc.identifier.issn0894-1491-
dc.identifier.urihttp://hdl.handle.net/10261/35145-
dc.descriptionEl pdf del artículo es la versión post-print.es_ES
dc.description.abstractShort interfering RNA (siRNA) inhibits the synthesis of specific proteins through RNA interference (RNAi). However, siRNA can induce innate immune responses that are mediated by toll-like receptors (TLRs) in cells of the immune system. Here, we sought to evaluate whether siRNA can induce such responses in glial cells. We examined the effects of various siRNA sequences prepared with lipids (oligofectamine). Lipid-siRNA induced variable degrees of silencing-independent nonspecific effects, e.g. increased Stat1 and Cox-2 expression and release of IL-6 and IP-10 in primary astroglia. This was prevented through chemical modification of siRNA by nucleoside 2′-O-methylation, without impairing specific gene silencing. Lipid-siRNA also induced nonspecific responses in purified astroglia, but not in microglia, or 3T3 cells. The highest TLR7 and TLR3 mRNA expression was found in microglia and purified astroglia, respectively. Accordingly, the TLR3 agonist poly(I:C) (PIC) induced higher release of IFN-β in primary and purified astroglia than in microglia. As siRNA, PIC induced IP-10, Stat1, VCAM-1, and Cox-2 and increased TLR3 mRNA expression. The effects of lipid-siRNA in purified astrocytes were attenuated after silencing TLR3 or TLR7 expression, and by the PKR inhibitor 2-aminopurine. Furthermore, lipid-siRNA induced the expression of RIG-I. In contrast, siRNA devoid of lipids did not enter the astrocytes, did not silence gene expression, and did not induce Stat1 or Cox-2. The results show that, in astroglia, lipid-siRNA induces innate immune responses that are mediated, at least in part, by intracellular mechanism dependent on TLR7, TLR3, and helicases.es_ES
dc.description.sponsorshipFunded by: National Grant from CICYT. Grant Number: SAF2005-05793; European Network of Excellence DiMI. Grant Number: LSHB-CT-2005-512146 and IDIBAPS.-
dc.language.isoenges_ES
dc.publisherWiley-Blackwelles_ES
dc.relation.isversionofPostprint-
dc.rightsopenAccesses_ES
dc.subjectGliaes_ES
dc.subjectTLR3es_ES
dc.subjectTLR7es_ES
dc.subjectHelicaseses_ES
dc.subjectStat1es_ES
dc.titleAstrocytes are very sensitive to develop innate immune responses to lipid-carried short interfering RNAes_ES
dc.typeartículoes_ES
dc.identifier.doi10.1002/glia.20738-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1002/glia.20738/fulles_ES
dc.identifier.e-issn1098-1136-
dc.identifier.pmid18709661-
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