| Protection against TNFα-dependent liver toxicity by intraperitoneal liposome delivered DsiRNA targeting TNFα in vivo. | |
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MedLine Citation:
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PMID: 22094102 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Tumor necrosis factor-alpha (TNFα) is a classic proinflammatory cytokine implicated in the pathogenesis of several autoimmune and inflammatory diseases including viral encephalitis. Macrophages being major producers of TNFα are thus attractive targets for in vivo RNA interference (RNAi) mediated down regulation of TNFα. The application of RNAi technology to in vivo models however presents obstacles, including rapid degradation of RNA duplexes in plasma, insufficient delivery to the target cell population and toxicity associated with intravenous administration of synthetic RNAs and carrier compounds. We exploited the phagocytic ability of macrophages for delivery of Dicer-substrate small interfering RNAs (DsiRNAs) targeting TNFα (DsiTNFα) by intraperitoneal administration of lipid-DsiRNA complexes that were efficiently taken up by peritoneal macrophages and other phagocytic cells. We report that DsiTNFα-lipid complexes delivered intraperitoneally altered the disease outcome in an acute sepsis model. Down-regulation of TNFα in peritoneal CD11b+ monocytes reduced liver damage in C57BL/6 mice and significantly delayed acute mortality in mice treated with low dose LPS plus d-galactosamine (D-GalN). |
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Authors:
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Patric Lundberg; Hui-Jung Yang; Seung-Jae Jung; Mark A Behlke; Scott D Rose; Edouard M Cantin |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-7 |
Journal Detail:
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Title: Journal of controlled release : official journal of the Controlled Release Society Volume: - ISSN: 1873-4995 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8607908 Medline TA: J Control Release Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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Division of Immunology, Beckman Research Institute at City of Hope National Medical Center, Duarte, CA, USA; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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