| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Published online before print April 9, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, California;
MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom; and
Isis Pharmaceuticals, Inc., Carlsbad Research Center, California
1Correspondence: The Scripps Research Institute, Departments of Immunology & Cell Biology, 10550 North Torrey Pines Road, CVN-18, La Jolla, CA 92037. E-mail: nmackman{at}scripps.edu
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 
(TNF-) 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- 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.
Key Words: gene regulation • coagulation • glucocorticoid
This article has been cited by other articles:
|
|
 |
|
  V. Douard, H.-I. Choi, S. Elshenawy, D. Lagunoff, and R. P. Ferraris Developmental reprogramming of rat GLUT5 requires glucocorticoid receptor translocation to the nucleus J. Physiol., August 1, 2008; 586(15): 3657 - 3673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Mogensen, R. S. Berg, S. R. Paludan, and L. Ostergaard Mechanisms of Dexamethasone-Mediated Inhibition of Toll-Like Receptor Signaling Induced by Neisseria meningitidis and Streptococcus pneumoniae Infect. Immun., January 1, 2008; 76(1): 189 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. de Kruif, L. C. Lemaire, I. A. Giebelen, M. A. D. van Zoelen, J. M. Pater, P. S. van den Pangaart, A. P. Groot, A. F. de Vos, P. J. Elliott, J. C. M. Meijers, et al. Prednisolone Dose-Dependently Influences Inflammation and Coagulation during Human Endotoxemia J. Immunol., February 1, 2007; 178(3): 1845 - 1851. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Cai, C. Song, I. Endoh, J. Goyette, W. Jessup, S. B. Freedman, H. P. McNeil, and C. L. Geczy Serum Amyloid A Induces Monocyte Tissue Factor J. Immunol., February 1, 2007; 178(3): 1852 - 1860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. BelAiba, T. Djordjevic, S. Bonello, F. Artunc, F. Lang, J. Hess, and A. Gorlach The Serum- and Glucocorticoid-Inducible Kinase Sgk-1 Is Involved in Pulmonary Vascular Remodeling: Role in Redox-Sensitive Regulation of Tissue Factor by Thrombin Circ. Res., March 31, 2006; 98(6): 828 - 836. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
