Linked Life Data

19896992

Source:http://linkedlifedata.com/resource/pubmed/id/19896992

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-12-9
pubmed:abstractText
Adenovirus (Ad)-based vectors have been utilized in human gene transfer clinical trials since 1993. Unfortunately, innate immune responses directed against the Ad capsid and/or its genetic cargo can significantly limit the usage of Ad vectors. Previous studies have demonstrated that several signaling pathways are triggered by Ads, inclusive of TLR-dependent pathways. The G-protein-coupled receptor adaptors beta-arrestin-1 (beta-Arr1) and beta-arrestin-2 (beta-Arr2) are known to have pivotal roles in regulating TLR4 triggered signaling and inflammatory responses. In this study, we examined the role of beta-arrestins in Ad5-vector-induced inflammatory responses. Our studies reveal that both beta-arrestins are capable of modulating Ad5-vector-induced inflammatory responses in vivo and in vitro. Importantly, our studies divulge another level of complexity to these responses, as our results demonstrate beta-Arr1 to be a positive regulator, and beta-Arr2 a negative regulator of Ad5 induced innate immune responses. These data may allow gene therapy biologists to more accurately study the mechanisms underlying Ad5-vector-induced immune responses, and may also direct future efforts to modulate these mechanisms to improve the safety and/or efficacy of this important gene transfer vector.
pubmed:grant
http://linkedlifedata.com/resource/pubmed/grant/P01 CA078673, http://linkedlifedata.com/resource/pubmed/grant/P01 CA078673-090006, http://linkedlifedata.com/resource/pubmed/grant/R01 AR056680-01A2, http://linkedlifedata.com/resource/pubmed/grant/R01 AR056680-02, http://linkedlifedata.com/resource/pubmed/grant/R01 AR056680-03, http://linkedlifedata.com/resource/pubmed/grant/R01 DK069884-04, http://linkedlifedata.com/resource/pubmed/grant/R01 HL095637-01, http://linkedlifedata.com/resource/pubmed/grant/R01 HL095637-02, http://linkedlifedata.com/resource/pubmed/grant/R01 HL095637-03, http://linkedlifedata.com/resource/pubmed/grant/R01AR056680, http://linkedlifedata.com/resource/pubmed/grant/R01DK-069884, http://linkedlifedata.com/resource/pubmed/grant/R01HL095637, http://linkedlifedata.com/resource/pubmed/grant/R21 AR055726-01A1, http://linkedlifedata.com/resource/pubmed/grant/R21AR055726
pubmed:commentsCorrections
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pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1872-7492
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
147
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
123-34
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
beta-Arrestins modulate Adenovirus-vector-induced innate immune responses: differential regulation by beta-arrestin-1 and beta-arrestin-2.
pubmed:affiliation
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, United States.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural