PMID- 15075360
OWN - NLM
STAT- MEDLINE
DCOM- 20040803
LR  - 20181130
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 76
IP  - 1
DP  - 2004 Jul
TI  - Dexamethasone enhances LPS induction of tissue factor expression in human 
      monocytic cells by increasing tissue factor mRNA stability.
PG  - 145-51
AB  - Glucocorticoids, such as dexamethasone (Dex), are used clinically in the 
      treatment of various inflammatory diseases. Dex acts by inhibiting the expression 
      of inflammatory mediators, such as tumor necrosis factor alpha (TNF-alpha) and 
      monocyte chemoattractant protein-1 (MCP-1). It is surprising that Dex enhances 
      bacterial lipopolysaccharide (LPS) induction of tissue factor (TF) expression in 
      human monocytic cells. TF is a transmembrane glycoprotein that activates the 
      coagulation protease cascade. In this study, we analyze the mechanism by which 
      Dex enhances LPS-induced TF expression in human monocytic cells. We found that 
      Dex reduced LPS-induced TF gene transcription but increased the stability of TF 
      mRNA. Dex decreased the stability of MCP-1 mRNA and did not affect TNF-alpha mRNA 
      stability. Finally, we showed that Dex increased the stability of a transcript 
      consisting of the final 297 nucleotides of the TF mRNA in in vitro decay assays. 
      This region contains AU-rich elements that regulate mRNA stability and may 
      mediate the Dex response. Therefore, despite an inhibition of TF gene 
      transcription, Dex enhances TF expression in human monocytic cells by increasing 
      the stability of TF mRNA.
FAU - Reddy, K Veera
AU  - Reddy KV
AD  - Department of Immunology, The Scripps Research Institute, 10550 North Torrey 
      Pines Road, CVN-18, La Jolla, CA 92037, USA.
FAU - Bhattacharjee, Gourab
AU  - Bhattacharjee G
FAU - Schabbauer, Gernot
AU  - Schabbauer G
FAU - Hollis, Angela
AU  - Hollis A
FAU - Kempf, Kevin
AU  - Kempf K
FAU - Tencati, Michael
AU  - Tencati M
FAU - O'Connell, Maria
AU  - O'Connell M
FAU - Guha, Mausumee
AU  - Guha M
FAU - Mackman, Nigel
AU  - Mackman N
LA  - eng
GR  - HL48872/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040409
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glucocorticoids)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 9035-58-9 (Thromboplastin)
SB  - IM
MH  - Base Sequence
MH  - Blotting, Northern
MH  - Cells, Cultured
MH  - *Chemokine CCL2
MH  - Dexamethasone/*pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Glucocorticoids/*pharmacology
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Molecular Sequence Data
MH  - Monocytes/*drug effects/metabolism
MH  - Polymerase Chain Reaction
MH  - Protein Biosynthesis
MH  - Proteins/drug effects
MH  - RNA Stability/*drug effects
MH  - RNA, Messenger/*metabolism
MH  - Thromboplastin/*biosynthesis/drug effects
MH  - Transcription, Genetic/drug effects
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/biosynthesis/drug effects
EDAT- 2004/04/13 05:00
MHDA- 2004/08/04 05:00
CRDT- 2004/04/13 05:00
PHST- 2004/04/13 05:00 [pubmed]
PHST- 2004/08/04 05:00 [medline]
PHST- 2004/04/13 05:00 [entrez]
AID - jlb.0204068 [pii]
AID - 10.1189/jlb.0204068 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2004 Jul;76(1):145-51. doi: 10.1189/jlb.0204068. Epub 2004 Apr 9.