Transcriptional and translational control of TNF-alpha gene expression in human monocytes by major histocompatibility complex class II ligands

Details

Serval ID
serval:BIB_FA09EA699923
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Transcriptional and translational control of TNF-alpha gene expression in human monocytes by major histocompatibility complex class II ligands
Journal
European Journal of Immunology
Author(s)
Espel  E., Garcia-Sanz  J. A., Aubert  V., Menoud  V., Sperisen  P., Fernandez  N., Spertini  F.
ISSN
0014-2980 (Print)
Publication state
Published
Issued date
10/1996
Volume
26
Number
10
Pages
2417-24
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct
Abstract
While non-stimulated primary human monocytes exhibit very low levels of tumor necrosis factor (TNF)-alpha mRNA, direct binding of the staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) to major histocompatibility complex (MHC) class II molecules results in a fast (peak 1 h after stimulation), transient induction (sevenfold) of TNF-alpha mRNA. This induction correlates with a fourfold increase in transcription rates of the TNF-alpha gene, as detected by run-on assays, and does not require de novo protein synthesis. Mapping of DNase-I hypersensitive sites (DHS) discloses two constitutive DHS, one located far upstream (within the TNF-beta promoter) and the other centered at -39 +/- 40 bp relative to the major TNF-alpha transcription start site, suggesting that the TNF-alpha gene was transcriptionally competent even prior to MHC class II engagement. Furthermore, stimulation of human monocytes with either TSST-1 or lipopolysaccharide increases the translational efficiency of TNF-alpha mRNA, as shown by a shift in the distribution of this mRNA species in polysome gradients and the translation rates of TNF-alpha measured by immunoprecipitation from cells pulsed with [35S] methionine. The increase in translation efficiency of TNF-alpha mRNA is independent of the half-life of TNF-alpha transcripts, which under the conditions used is unchanged. Taken together, our data indicate that TNF-alpha expression is tightly regulated by MHC class II ligands, both at the transcriptional and translational levels.
Keywords
*Bacterial Toxins Deoxyribonuclease I/diagnostic use Enterotoxins/*pharmacology Gene Expression Regulation/drug effects Histocompatibility Antigens Class II/physiology Humans Ligands Lipopolysaccharides/pharmacology Monocytes/*physiology Polyribosomes/metabolism Promoter Regions (Genetics) Protein Biosynthesis RNA, Messenger/genetics Signal Transduction Staphylococcus aureus/immunology Superantigens/pharmacology Transcription, Genetic Tumor Cells, Cultured Tumor Necrosis Factor-alpha/*genetics
Pubmed
Web of science
Create date
25/01/2008 15:20
Last modification date
20/08/2019 16:25
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