Linked Life Data

21454695

Source:http://linkedlifedata.com/resource/pubmed/id/21454695

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2011-6-27
pubmed:abstractText
Transcription factor NF-?B is persistently activated in many chronic inflammatory diseases and cancers. The short term regulation of NF-?B is well understood, but little is known about the mechanisms of its long term activation. We studied the effect of a single application of TNF-? on NF-?B activity for up to 48 h in intestinal epithelial cells. Results show that NF-?B remained persistently activated up to 48 h after TNF-? and that the long term activation of NF-?B was accompanied by a biphasic degradation of I?B?. The first phase of I?B? degradation was proteasome-dependent, but the second was not. Further investigation showed that TNF-? stimulated formation of autophagosomes in intestinal epithelial cells and that I?B? co-localized with autophagosomal vesicles. Pharmacological or genetic blockade of autophagosome formation or the inhibition of lysosomal proteases decreased TNF-?-induced degradation of I?B? and lowered NF-?B target gene expression. Together, these findings indicate a role of autophagy in the control of long term NF-?B activity. Because abnormalities in autophagy have been linked to ineffective innate immunity, we propose that alterations in NF-?B may mediate this effect.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22886-93
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Autophagosomal IkappaB alpha degradation plays a role in the long term control of tumor necrosis factor-alpha-induced nuclear factor-kappaB (NF-kappaB) activity.
pubmed:affiliation
Department of Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't