Results
Your Query
▶
▶
Subject | Predicate | Object |
---|---|---|
http://purl.uniprot.org/citations/27911957 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/27911957 | http://www.w3.org/2000/01/rdf-schema#comment | "RationaleTumor necrosis factor-alpha (TNF-α) is a potent pro-inflammatory mediator and its expression is up-regulated in chronic obstructive pulmonary disease (COPD). Tristetraprolin (TTP) is implicated in regulation of TNF-α expression; however, whether TTP is involved in cigarette smoke-induced TNF-α expression has not been determined.MethodsTTP expression was examined by western blot analysis in murine alveolar macrophages and alveolar epithelial cells challenged without or with cigarette smoke extract (CSE). TNF-α mRNA stability, and the decay of TNF-α mRNA, were determined by real-time quantitative RT-PCR. TNF-α protein levels were examined at the same time in these cells. To identify the molecular mechanism involved, a construct expressing the human beta-globin reporter mRNA containing the TNF-α 3'-untranslated region was generated to characterize the TTP targeted site within TNF-α mRNA.ResultsCSE induced TTP down-regulation in alveolar macrophages and alveolar epithelial cells. Reduced TTP expression resulted in significantly increased TNF-α mRNA stability. Importantly, increased TNF-α mRNA stability due to impaired TTP function resulted in significantly increased TNF-α levels in these cells. Forced TTP expression abrogated the increased TNF-α mRNA stability and expression induced by CSE. By using the globin reporter construct containing TNF-α mRNA 3'-untranslated region, the data indicate that TTP directly targets the adenine- and uridine-rich region (ARE) of TNF-α mRNA and negatively regulates TNF-α expression at the post-transcriptional level.ConclusionThe data demonstrate that cigarette smoke exposure reduces TTP expression and impairs TTP function, resulting in significantly increased TNF-α mRNA stability and excessive TNF-α expression in alveolar macrophages and epithelial cells. The data suggest that TTP is a novel post-transcriptional regulator and limits excessive TNF-α expression and inflammatory response induced by cigarette smoke."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0167451"xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Chen C.Y."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Han X."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Che P."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Hu M."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Li H."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Luo Y."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Zhang Q."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Zhou Y."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Wells J.M."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Cai G."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Ding Q."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Cheng M.L."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Steele C."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Blalock J.E."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Mu M."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Jackson P.L."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Thannickal V.J."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Zhao X.K."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Liang Y.D."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Gao C.Q."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/author | "Luo X.H."xsd:string |
http://purl.uniprot.org/citations/27911957 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |