Document Detail

Negative regulation of IL-1beta production at the level of transcription in macrophages stimulated with LPS.
MedLine Citation:
PMID:  11683585     Owner:  NLM     Status:  MEDLINE    
The IL-1beta gene is rapidly and transiently expressed in LPS-stimulated macrophages. While several studies have addressed the molecular basis of LPS-induced transcriptional activity, the mechanisms which underlie the subsequent decrease in IL-1beta gene expression have not been as extensively examined. In this regard, we found that the characteristic decrease in IL-1beta production after LPS stimulation could be abrogated by treatment of macrophages with the protein kinase inhibitor staurosporine. This inhibitor mediated an enhancement of IL-1beta production which was first evident 8-12 h after LPS stimulation and continued at peak levels for the rest of the incubation period (24 h). IL-1beta production was correlated with the level of mRNA specific for the cytokine. Staurosporine also mediated an enhancement of LPS-induced IL-1beta promoter activity measured in RAW 264.7 cells transiently transfected with an IL-1beta reporter plasmid. This increase paralleled the enhancement of IL-1beta mRNA by staurosporine both in intensity and time after LPS stimulation, suggesting that the negative regulation of IL-1beta is exerted primarily at the level of transcription. This regulation may be at least partially due to an observed inhibition of nitric oxide production by staurosporine in LPS-activated macrophages, which was correlated with enhanced IL-1beta production. However, the intensity of the observed effects suggested that additional staurosporine-sensitive regulatory mechanisms are in operation at the level of promoter activity.
D Schilling; T Beissert; M J Fenton; K Nixdorff
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cytokine     Volume:  16     ISSN:  1043-4666     ISO Abbreviation:  Cytokine     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-30     Completed Date:  2002-02-25     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9005353     Medline TA:  Cytokine     Country:  United States    
Other Details:
Languages:  eng     Pagination:  51-61     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Department of Microbiology and Genetics, Darmstadt University of Technology, Schnittspahnstrasse 10, D-64287 Darmstadt, Germany.
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MeSH Terms
Cell Line
Enzyme Inhibitors / pharmacology
Genes, Reporter
Interleukin-1 / biosynthesis*,  genetics
Lipopolysaccharides / pharmacology*
Macrophage Activation*
Macrophages / drug effects,  immunology*
Mice, Inbred C57BL
NF-kappa B / metabolism
Nitric Oxide / biosynthesis
Promoter Regions, Genetic / drug effects
RNA Stability
Recombinant Fusion Proteins / metabolism
Staurosporine / pharmacology
Time Factors
Transcription, Genetic*
Tumor Necrosis Factor-alpha / metabolism
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Interleukin-1; 0/Lipopolysaccharides; 0/NF-kappa B; 0/Recombinant Fusion Proteins; 0/Tumor Necrosis Factor-alpha; 10102-43-9/Nitric Oxide; 62996-74-1/Staurosporine

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