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Human tumor necrosis factor-alpha gene 3' untranslated region confers inducible toxin responsiveness to homologous promoter in monocytic THP-1 cells.

  • Seiler-Tuyns A Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.
  • Dufour N
  • Spertini F
  • 1999-07-27
Published in:
  • The Journal of biological chemistry. - 1999
3' Untranslated Regions
Actins
Animals
Bacterial Toxins
Cell Line
Chickens
Cytomegalovirus
Enterotoxins
Gene Expression Regulation
Genes, Immediate-Early
Genes, Reporter
Globins
Humans
Lipopolysaccharides
Monocytes
Promoter Regions, Genetic
Rabbits
Recombinant Fusion Proteins
Reverse Transcriptase Polymerase Chain Reaction
Superantigens
Transcription, Genetic
Transfection
Tumor Necrosis Factor-alpha
English To better define the role of 3' untranslated region (3'UTR) on transcriptional regulation of the human tumor necrosis factor (TNF)-alpha gene, monocytic human THP-1 cells were transfected with two TNF-alpha promoter constructs spanning base pairs -1897/-1 and -1214/-1, respectively, and linked to the rabbit beta-globin gene. Quantitative globin gene expression of chimerae was measured by reverse transcription-polymerase chain reaction. A construct linking the chicken beta-actin promoter and a deleted portion of the beta-globin gene was cotransfected and used as internal standard. Unexpectedly, when THP-1 cells were stimulated with lipopolysaccharide or toxic shock syndrome toxin-1, gene regulation was hardly detected. In contrast, endogenous TNF-alpha gene regulation measured by the same reverse transcription-polymerase chain reaction procedure was vigorous. Remarkably, ligation of 3'UTR to chimeric constructs led to a drastic drop in the basal level of chimeric gene expression, resulting in a 15- to 40-fold induction of the reporter gene. Consistently, when the TNF-alpha promoter was replaced by the cytomegalovirus early immediate promoter, gene expression was also uniformly reduced but was no longer up-regulated upon stimulation with lipopolysaccharide and toxic shock syndrome toxin-1. These data provide the first line of evidence that, in addition to its role in TNF-alpha transcript stability and translation, human TNF-alpha 3'UTR also participates in modulating gene expression at the transcriptional level.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.rero.ch/global/documents/137149
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