Linked Life Data

18211505

Source:http://linkedlifedata.com/resource/pubmed/id/18211505

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-1-23
pubmed:abstractText
Overcoming cell-mediated immunity, especially of human CD8(+) CTLs, is important for the success of xenotransplantation. Our group has previously reported that the cytotoxicity of human CD8(+) CTLs against pig endothelial cells (PEC) is highly detrimental and mediated in major part by the Fas/FasL apoptotic pathway. Cellular FLICE inhibitory protein (c-FLIP) was originally identified as an inhibitor of death-receptor signaling through binding competition with caspase-8 for recruitment to Fas-associated via death domain (FADD). Two major c-FLIP variants result from alternative mRNA splicing: a short, 26-KDa protein (c-FLIP(S)) and a long, 55-KDa form (c-FLIP(L)). The cytoprotective effects of c-FLIP(S/L) in xenograft cells remain controversial. This study demonstrates that the overexpression of c-FLIP(S/L) genes markedly suppress human CD8(+) CTL-mediated xenocytotoxicity and, in addition, the cytoprotective effects of c-FLIP(L) appear to be significantly stronger than those of c-FLIP(S). Furthermore, to prove the prolonged effects of xenograft survival, PEC transfectants with c-FLIP(S/L) genes were transplanted under rat kidney capsules. Prolonged survival was elicited from FLIP(S/L) transfectants, whereas parental PEC was completely rejected through day 5, posttransplant. Thus, intracellular remodeling with the overexpression of c-FLIP(S/L) in xenograft cells may avoid innate cellular attacks against xenografts and facilitate long-term xenograft survival.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1600-6143
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
288-97
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
In vitro and in vivo prevention of human CD8+ CTL-mediated xenocytotoxicity by pig c-FLIP expression in porcine endothelial cells.
pubmed:affiliation
Department of Surgery (E1), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. tanemura@surg1.med.osaka-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't