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PMID: 1875949 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Tissue factor mRNA in THP-1 monocytic cells is regulated at both transcriptional and posttranscriptional levels in response to lipopolysaccharide.

Molecular and cellular biology ·Vol. 11 ·No. 9 ·1991-09-00 ·Pages 4732-8

Brand K, Fowler BJ, Edgington TS, Mackman N

Abstract

Tissue factor (TF) is transiently expressed in human monocytes exposed to the inflammatory agonist bacterial lipopolysaccharide (LPS). Since TF is the major cellular initiator of the coagulation protease cascades, it is inferred that its expression within the vasculature is strictly regulated. In this study, we investigated mechanisms which control TF mRNA expression in the human monocytic cell line THP-1. LPS induced a rapid and transient accumulation of the mature 2.2-kb TF mRNA, which was maximal at 2 h. After stimulation, the rate of transcription of the TF gene was increased (3.3 +/- 1.3)fold. In addition, we observed a significant change in TF mRNA stability: at 1 h after LPS stimulation, TF mRNA was stable during a 60-min period and had a half-life of greater than 120 min, whereas at 2 h, the half-life had declined to 25 +/- 5 min. Furthermore, a larger (3.4-kb) TF RNA species was induced in these cells; the size of this species and data from selective hybridizations with intron-specific probes are consistent with the presence of an unspliced copy of intron 1. These results demonstrate that the LPS-induced accumulation of TF mRNA levels in these monocytic cells is accomplished by both transcriptional and posttranscriptional control mechanisms.

Related Genes
TF
MeSH Terms
Cycloheximide/pharmacology Gene Expression Regulation/drug effects Humans Kinetics Leukemia, Myeloid Lipopolysaccharides/pharmacology RNA Processing, Post-Transcriptional RNA, Messenger/biosynthesis Thromboplastin/genetics Transcription, Genetic Tumor Cells, Cultured
Chemicals
Lipopolysaccharides RNA, Messenger Thromboplastin Cycloheximide
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Brand K
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Fowler B J
Edgington T S
Mackman N
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.11.9.4732-4738.1991
Published
1991-09-00
Pages
4732-8
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC361371
Subset
IM
Grants
NHLBI NIH HHS · P01 HL-16411 · United States
External Links
PubMed source DOI: 10.1128/mcb.11.9.4732-4738.1991 PMC Full Text View journal details
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