Source:http://linkedlifedata.com/resource/pubmed/id/18786178
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2008-11-7
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pubmed:abstractText |
We recently reported that bcl-xL regulates interleukin 8 (CXCL8) protein expression and promoter activity in glioblastoma cells. In this paper we demonstrate that CXCL8 induction by bcl-xL is mediated through a nuclear factor-kappa B (NF-kB)-dependent mechanism. Mutational studies on the CXCL8 promoter showed that NF-kB binding site was required for bcl-xL-induced promoter activity and an enhanced nuclear expression of NF-kB subunits p65 and p50 was observed after bcl-xL over-expression. Electrophoretic mobility shift assay showed an increased DNA-binding activity of NF-kB in bcl-xL over-expressing cells and the use of specific antibodies confirmed the involvement of p65 and p50 in NF-kB activity on CXCL8 promoter sequence. NF-kB activity regulation by bcl-xL involved IkBalpha and IKK complex signaling pathway. In fact, bcl-xL over-expression induced a decrease of cytoplasmic expression of the IkBalpha protein, paralleled by an increase in the phosphorylation of the same IkBalpha and IKKalpha/beta. Moreover, the down-regulation of the ectopic or endogenous bcl-xL expression through RNA interference confirmed the ability of bcl-xL to modulate NF-kB pathway, and the transient expression of a degradation-resistant form of the cytoplasmic NF-kB inhibitor IkBalpha in bcl-xL transfectants confirmed the involvement of that inhibitor in bcl-xL-induced CXCL8 expression and promoter activity. In conclusion, our results demonstrate the role of NF-kB as the mediator of bcl-xL-induced CXCL8 up-regulation in glioblastoma cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1471-4159
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
107
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
871-82
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pubmed:meshHeading |
pubmed-meshheading:18786178-Blotting, Western,
pubmed-meshheading:18786178-Cell Line, Tumor,
pubmed-meshheading:18786178-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:18786178-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:18786178-Gene Expression Regulation,
pubmed-meshheading:18786178-Glioblastoma,
pubmed-meshheading:18786178-Humans,
pubmed-meshheading:18786178-Interleukin-8,
pubmed-meshheading:18786178-NF-kappa B,
pubmed-meshheading:18786178-Neovascularization, Pathologic,
pubmed-meshheading:18786178-Promoter Regions, Genetic,
pubmed-meshheading:18786178-Signal Transduction,
pubmed-meshheading:18786178-Transfection,
pubmed-meshheading:18786178-Up-Regulation,
pubmed-meshheading:18786178-bcl-X Protein
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pubmed:year |
2008
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pubmed:articleTitle |
Involvement of nuclear factor-kappa B in bcl-xL-induced interleukin 8 expression in glioblastoma.
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pubmed:affiliation |
Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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