Dataset Information
Tristetraprolin Down-Regulation Contributes to Persistent TNF-Alpha Expression Induced by Cigarette Smoke Extract through a Post-Transcriptional Mechanism.
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ABSTRACT: Rationale
Tumor necrosis factor-alpha (TNF-?) 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-? expression; however, whether TTP is involved in cigarette smoke-induced TNF-? expression has not been determined.Methods
TTP expression was examined by western blot analysis in murine alveolar macrophages and alveolar epithelial cells challenged without or with cigarette smoke extract (CSE). TNF-? mRNA stability, and the decay of TNF-? mRNA, were determined by real-time quantitative RT-PCR. TNF-? 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-? 3'-untranslated region was generated to characterize the TTP targeted site within TNF-? mRNA.Results
CSE induced TTP down-regulation in alveolar macrophages and alveolar epithelial cells. Reduced TTP expression resulted in significantly increased TNF-? mRNA stability. Importantly, increased TNF-? mRNA stability due to impaired TTP function resulted in significantly increased TNF-? levels in these cells. Forced TTP expression abrogated the increased TNF-? mRNA stability and expression induced by CSE. By using the globin reporter construct containing TNF-? mRNA 3'-untranslated region, the data indicate that TTP directly targets the adenine- and uridine-rich region (ARE) of TNF-? mRNA and negatively regulates TNF-? expression at the post-transcriptional level.Conclusion
The data demonstrate that cigarette smoke exposure reduces TTP expression and impairs TTP function, resulting in significantly increased TNF-? mRNA stability and excessive TNF-? expression in alveolar macrophages and epithelial cells. The data suggest that TTP is a novel post-transcriptional regulator and limits excessive TNF-? expression and inflammatory response induced by cigarette smoke.
SUBMITTER: Zhao XK
PROVIDER: S-EPMC5135108 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Publications
Tristetraprolin Down-Regulation Contributes to Persistent TNF-Alpha Expression Induced by Cigarette Smoke Extract through a Post-Transcriptional Mechanism.
PloS one 20161202 12
<h4>Rationale</h4>Tumor 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.<h4>Methods</h4>TTP expression was examined by western blot analysis in murine alveolar macrophages and alveolar epithelial cells challenged without or ...[more]
