Statements in which the resource exists as a subject.
PredicateObject
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.