Source:http://linkedlifedata.com/resource/pubmed/id/14530362
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
|
pubmed:dateCreated |
2003-10-7
|
pubmed:abstractText |
During inflammatory responses, a major posttranscriptional regulation of early response and inflammatory gene expression occurs through modulation of mRNA turnover. We report that two potent inducers of the CC chemokine eotaxin, TNF-alpha and IL-4, regulate its production in airway epithelial cells by increasing eotaxin mRNA stability. In experiments using the transcriptional inhibitor actinomycin D, eotaxin mRNA half-life was significantly prolonged by cell stimulation with TNF-alpha or IL-4, with the combination of the two cytokines being the most effective in extending the mRNA half-life. Involvement of the eotaxin 3' untranslated region in the mRNA-stabilizing effect was tested by transient transfection of a construct expressing a chimeric transcript carrying a serum-inducible beta-globin reporter linked to the eotaxin 3' untranslated region. The half-life of the chimeric mRNA was markedly increased in cells stimulated with TNF-alpha and IL-4. Evidence that the mRNA-stabilizing protein HuR participated in the cytokine effect was obtained: first, HuR presence in the cytoplasm, believed to be required for HuR-mediated mRNA stabilization, increased in both transformed (BEAS-2B cell line) and primary bronchial epithelial cells following treatment with TNF-alpha and IL-4. Second, endogenous eotaxin mRNA was found to bind to HuR in vivo, as detected by immunoprecipitation of HuR-containing messenger ribonucleoprotein complexes followed by real-time RT-PCR analysis; such association increased after cell treatment with TNF-alpha and IL-4. Third, overexpression of HuR in BEAS-2B cells significantly increased the expression of eotaxin mRNA and protein. Our findings implicate mRNA stabilization in the cytokine-mediated increase in eotaxin expression and strongly suggest a role for HuR in this effect.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
AIM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Surface,
http://linkedlifedata.com/resource/pubmed/chemical/CCL11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ccl11 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL11,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CC,
http://linkedlifedata.com/resource/pubmed/chemical/Drug Combinations,
http://linkedlifedata.com/resource/pubmed/chemical/ELAVL1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
|
pubmed:status |
MEDLINE
|
pubmed:month |
Oct
|
pubmed:issn |
0022-1767
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
171
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
4369-78
|
pubmed:dateRevised |
2011-11-17
|
pubmed:meshHeading |
pubmed-meshheading:14530362-3' Untranslated Regions,
pubmed-meshheading:14530362-Animals,
pubmed-meshheading:14530362-Antigens, Surface,
pubmed-meshheading:14530362-Base Sequence,
pubmed-meshheading:14530362-Bronchi,
pubmed-meshheading:14530362-Cell Line, Transformed,
pubmed-meshheading:14530362-Chemokine CCL11,
pubmed-meshheading:14530362-Chemokines, CC,
pubmed-meshheading:14530362-Drug Combinations,
pubmed-meshheading:14530362-Gene Expression Regulation,
pubmed-meshheading:14530362-Humans,
pubmed-meshheading:14530362-Interleukin-4,
pubmed-meshheading:14530362-Mice,
pubmed-meshheading:14530362-Molecular Sequence Data,
pubmed-meshheading:14530362-NIH 3T3 Cells,
pubmed-meshheading:14530362-RNA, Messenger,
pubmed-meshheading:14530362-RNA Stability,
pubmed-meshheading:14530362-RNA-Binding Proteins,
pubmed-meshheading:14530362-Respiratory Mucosa,
pubmed-meshheading:14530362-Tumor Necrosis Factor-alpha,
pubmed-meshheading:14530362-Up-Regulation
|
pubmed:year |
2003
|
pubmed:articleTitle |
Regulation of eotaxin gene expression by TNF-alpha and IL-4 through mRNA stabilization: involvement of the RNA-binding protein HuR.
|
pubmed:affiliation |
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|