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PMID: 1744583 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Lipopolysaccharide-mediated transcriptional activation of the human tissue factor gene in THP-1 monocytic cells requires both activator protein 1 and nuclear factor kappa B binding sites.

The Journal of experimental medicine ·Vol. 174 ·No. 6 ·1991-12-01 ·Pages 1517-26

Mackman N, Brand K, Edgington TS

Abstract

Lipopolysaccharide (LPS) activation of cells of monocytic lineage leads to rapid and transient expression of a set of inflammatory gene products, including tissue factor (TF). This transmembrane receptor is the major cellular initiator of the blood coagulation cascades, and induced expression of TF is postulated to play a role in inflammation. Functional studies using transfected THP-1 monocytic cells revealed the presence of a 56-bp LPS response element (LRE) within the TF promoter that conferred LPS responsiveness to a heterologous promoter. LPS stimulation of these cells activated proteins that bound to nucleotide sequences within the LRE resembling consensus binding sites for activator protein 1 (AP-1) and nuclear factor kappa B (NF-kappa B). Induction of the TF gene may represent a prototypic example of gene activation in monocytic cells by assembly of transcription factor complexes, and may clarify the role of AP-1 and NF-kappa B in the regulation of other LPS-responsive genes.

MeSH Terms
Base Sequence Binding Sites Humans Lipopolysaccharides/metabolism Molecular Sequence Data Mutagenesis NF-kappa B/physiology Promoter Regions, Genetic Proto-Oncogene Proteins c-jun/physiology Thromboplastin/genetics Transcription, Genetic/drug effects Tumor Cells, Cultured Tumor Necrosis Factor-alpha/genetics
Chemicals
Lipopolysaccharides NF-kappa B Proto-Oncogene Proteins c-jun Tumor Necrosis Factor-alpha Thromboplastin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Mackman N
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Brand K
Edgington T S
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.174.6.1517
Published
1991-12-01
Pages
1517-26
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2119026
Subset
IM
Grants
NHLBI NIH HHS · HL-16411 · United States
NIMH NIH HHS · MH-47680 · United States
External Links
PubMed source DOI: 10.1084/jem.174.6.1517 PMC Full Text View journal details
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