Interactive effects of the tumor necrosis factor promoter and 3’-untranslated regions
Authors
Discussion
Loading...
Member takes
Implication
In vitro study reveals concerted control of TNF expression by promoter and 3'-UTR sequences in macrophages, highlighting distinct regulatory targets of anti-inflammatory inhibitors.
Key Points
- To determine how the TNF promoter and 3'-untranslated region coordinate TNF expression in macrophages and mediate responsiveness to endotoxin and inhibitory compounds.
- Generated chloramphenicol acetyltransferase reporter constructs containing the TNF promoter and 3'-untranslated region either individually or combined.
- Treated macrophages with bacterial endotoxin (LPS) alongside specific inhibitors, including dexamethasone, 2-aminopurine, pentoxifylline, and dibutyryl cAMP, to measure reporter activity and mRNA synthesis.
- The TNF promoter and 3'-untranslated region act in concert to induce TNF gene expression in macrophages, linking transcriptional activation with translational derepression upon endotoxin stimulation.
- Dexamethasone suppresses TNF synthesis at both transcription and translation via both the promoter and 3'-untranslated region, whereas 2-aminopurine acts exclusively through promoter sequences.
- Pentoxifylline suppression occurs partially at the level of transcription and strictly requires the presence of both the promoter and 3'-untranslated region.
Cite This Study
Han et al. (1991) studied this question.