Linked Life Data

21562857

Source:http://linkedlifedata.com/resource/pubmed/id/21562857

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2011-7-22
pubmed:abstractText
Type I interferons constitute a family of pleiotropic cytokines that have a key role in both adaptive and innate immunity. The interferon signalling pathways mediate transcriptional regulation of hundreds of genes, which result in mRNA degradation, decreased protein synthesis, cell cycle inhibition and induction of apoptosis. To elucidate regulatory networks important for interferon induced cell death, we generated interferon resistant U937 cells by selection in progressively increasing concentrations of interferon-? (IFN-?). The results show that IFN-? activates the death receptor signalling pathway and that IFN resistance was associated with cross-resistance to several death receptor ligands in a manner similar to previously described Fas resistant U937 cell lines. Increased expression of the long splice variant of the cellular FLICE-like inhibitor protein (cFLIP-L) was associated with the resistance to death receptor and IFN-? stimulation. Accordingly, inhibition of cFLIP-L expression with cycloheximide or through cFLIP short harpin RNA interference restored sensitivity to Fas and/or IFN-?. Thus, we now show that selection for interferon resistance can generate cells with increased expression of cFLIP, which protects the cells from both IFN-? and death receptor mediated apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1573-675X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
783-94
pubmed:meshHeading
pubmed-meshheading:21562857-Antibodies, pubmed-meshheading:21562857-Apoptosis, pubmed-meshheading:21562857-Apoptosis Regulatory Proteins, pubmed-meshheading:21562857-CASP8 and FADD-Like Apoptosis Regulating Protein, pubmed-meshheading:21562857-Caspase 8, pubmed-meshheading:21562857-Caspase 9, pubmed-meshheading:21562857-Cycloheximide, pubmed-meshheading:21562857-Drug Resistance, pubmed-meshheading:21562857-Enzyme Activation, pubmed-meshheading:21562857-Enzyme Assays, pubmed-meshheading:21562857-Gene Expression Regulation, pubmed-meshheading:21562857-Humans, pubmed-meshheading:21562857-Interferon-alpha, pubmed-meshheading:21562857-Interphase, pubmed-meshheading:21562857-RNA Interference, pubmed-meshheading:21562857-Receptors, Death Domain, pubmed-meshheading:21562857-U937 Cells, pubmed-meshheading:21562857-Up-Regulation
pubmed:year
2011
pubmed:articleTitle
Inhibition of cellular FLICE-like inhibitory protein abolishes insensitivity to interferon-? and death receptor stimulation in resistant variants of the human U937 cell line.
pubmed:affiliation
Department of Medical Chemistry and Biophysics, Umeå University, 90187 Umeå, Sweden. jeanette.blomberg@medchem.umu.se
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't