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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2009-7-16
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pubmed:abstractText |
Immune suppression is a major cause of morbidity and mortality in the patients with sepsis. Apoptotic loss of immune effector cells such as CD4 T and B cells is a key component in the loss of immune competence in sepsis. Inhibition of lymphocyte apoptosis has led to improved survival in animal models of sepsis. Using quantitative real-time polymerase chain reaction of isolated splenic CD4 T and B cells, we determined that Bim and PUMA, two key cell death proteins, are markedly upregulated during sepsis. Lymphocytes have been notoriously difficult to transfect with small interfering RNA (siRNA). Consequently a novel, cyclodextrin polymer-based, transferrin receptor-targeted, delivery vehicle was used to coadminister siRNA to Bim and PUMA to mice immediately after cecal ligation and puncture. Antiapoptotic siRNA-based therapy markedly decreased lymphocyte apoptosis and prevented the loss of splenic CD4 T and B cells. Flow cytometry confirmed in vivo delivery of siRNA to CD4 T and B cells and also demonstrated decreases in intracellular Bim and PUMA protein. In conclusion, Bim and PUMA are two critical mediators of immune cell death in sepsis. Use of a novel cyclodextrin polymer-based, transferrin receptor-targeted siRNA delivery vehicle enables effective administration of antiapoptotic siRNAs to lymphocytes and reverses the immune cell depletion that is a hallmark of this highly lethal disorder.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl-2-like protein 11,
http://linkedlifedata.com/resource/pubmed/chemical/Cellulose,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclodextrins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PUMA protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transferrin,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/cyclodextrin polymer
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1540-0514
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pubmed:author |
pubmed-author:BrahmamdamPavanP,
pubmed-author:ChangKatherine CKC,
pubmed-author:CoopersmithCraig MCM,
pubmed-author:HeidelJeremy DJD,
pubmed-author:HoekzemaAndrew SAS,
pubmed-author:HolemonHeatherH,
pubmed-author:HotchkissRichard SRS,
pubmed-author:McDonoughJacquelyn SJS,
pubmed-author:McDunnJonathan EJE,
pubmed-author:SchierdingWilliamW,
pubmed-author:UnsingerJacquelineJ,
pubmed-author:WatanabeEizoE,
pubmed-author:ZhouTony TTT
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pubmed:issnType |
Electronic
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
131-9
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pubmed:dateRevised |
2010-12-3
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pubmed:meshHeading |
pubmed-meshheading:19033888-Animals,
pubmed-meshheading:19033888-Apoptosis,
pubmed-meshheading:19033888-Apoptosis Regulatory Proteins,
pubmed-meshheading:19033888-B-Lymphocytes,
pubmed-meshheading:19033888-CD4-Positive T-Lymphocytes,
pubmed-meshheading:19033888-Cellulose,
pubmed-meshheading:19033888-Cyclodextrins,
pubmed-meshheading:19033888-Humans,
pubmed-meshheading:19033888-Lymphocyte Depletion,
pubmed-meshheading:19033888-Male,
pubmed-meshheading:19033888-Membrane Proteins,
pubmed-meshheading:19033888-Mice,
pubmed-meshheading:19033888-Proto-Oncogene Proteins,
pubmed-meshheading:19033888-RNA, Small Interfering,
pubmed-meshheading:19033888-Receptors, Transferrin,
pubmed-meshheading:19033888-Sepsis,
pubmed-meshheading:19033888-Transfection,
pubmed-meshheading:19033888-Tumor Suppressor Proteins
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pubmed:year |
2009
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pubmed:articleTitle |
Targeted delivery of siRNA to cell death proteins in sepsis.
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pubmed:affiliation |
Department of Surgery, Washington University in St Louis, School of Medicine, St Louis, Missouri 63110, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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