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
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
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