| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 36, 33471-33477, September 7, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Agonists via Inhibition
of CCAAT Box/Enhancer-binding Protein 
*
§**,,,
,,**
From the Fibrinogen is a coagulation factor
and an acute phase reactant up-regulated by inflammatory cytokines,
such as interleukin 6 (IL-6). Elevated plasma fibrinogen levels are
associated with coronary heart diseases. Fibrates are clinically
used hypolipidemic drugs that act via the nuclear receptor peroxisome
proliferator-activated receptor Département d'Athérosclerose,
U.545 INSERM, Institut Pasteur de Lille and Faculté de Pharmacie,
Université de Lille II, 59019 Lille, France, the
§ Gaubius Laboratory, TNO-Prevention and Health, P. O. Box
2215, 2301 CE Leiden, The Netherlands, ¶ U.459 INSERM,
Laboratoire de Biologie Cellulaire, Faculté de Médecine H. Warembourg, 59045 Lille Cédex, France, and the
Cardiology Research Complex, 721552 Moscow, Russia
(PPAR). In addition, most
fibrates also reduce plasma fibrinogen levels, but the molecular
mechanism is unknown. In this study, we demonstrate that fibrates
decrease basal and IL-6-stimulated expression of the human
fibrinogen-
gene in human primary hepatocytes and hepatoma HepG2
cells. Fibrates diminish basal and IL-6-induced fibrinogen- promoter
activity, and this effect is enhanced in the presence of co-transfected
PPAR. Site-directed mutagenesis experiments demonstrate that PPAR
activators decrease human fibrinogen- promoter activity via the
CCAAT box/enhancer-binding protein (C/EBP) response element.
Co-transfection of the transcriptional intermediary factor
glucocorticoid receptor-interacting protein 1/transcriptional intermediary factor 2 (GRIP1/TIF2) enhances fibrinogen- gene transcription and alleviates the repressive effect of PPAR.
Co-immunoprecipitation experiments demonstrate that PPAR and
GRIP1/TIF2 physically interact in vivo in human liver.
These data demonstrate that PPAR agonists repress human fibrinogen
gene expression by interference with the C/EBP pathway through
titration of the coactivator GRIP1/TIF2. We observed that the
anti-inflammatory action of PPAR is not restricted to fibrinogen but
also applies to other acute phase genes containing a C/EBP response
element; it also occurs under conditions in which the stimulating
action of IL-6 is potentiated by dexamethasone. These findings
identify a novel molecular mechanism of negative gene regulation by
PPAR and reveal the direct implication of PPAR in the modulation
of the inflammatory gene response in the liver.
This article has been cited by other articles:
|
|
 |
|
  C. J.F. de Wolf, R. M.J. Cupers, R. M. Bertina, and H. L. Vos Interleukin-6 Induction of Protein S Is Regulated Through Signal Transducer and Activator of Transcription 3 Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 2168 - 2174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Westra, J Bijzet, B Doornbos-van der Meer, M H van Rijswijk, and P C Limburg Differential influence of p38 mitogen activated protein kinase (MAPK) inhibition on acute phase protein synthesis in human hepatoma cell lines Ann Rheum Dis, July 1, 2006; 65(7): 929 - 935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cuzzocrea, E. Mazzon, R. Di Paola, A. Peli, A. Bonato, D. Britti, T. Genovese, C. Muia, C. Crisafulli, and A. P. Caputi The role of the peroxisome proliferator-activated receptor-{alpha} (PPAR-{alpha}) in the regulation of acute inflammation J. Leukoc. Biol., May 1, 2006; 79(5): 999 - 1010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zambon, P. Gervois, P. Pauletto, J.-C. Fruchart, and B. Staels Modulation of Hepatic Inflammatory Risk Markers of Cardiovascular Diseases by PPAR-{alpha} Activators: Clinical and Experimental Evidence Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 977 - 986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Staels and J.-C. Fruchart Therapeutic Roles of Peroxisome Proliferator-Activated Receptor Agonists Diabetes, August 1, 2005; 54(8): 2460 - 2470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Currie, V. Bombail, J. D. Oliver, D. J. Moore, F. L. Lim, V. Gwilliam, I. Kimber, K. Chipman, J. G. Moggs, and G. Orphanides Gene Ontology Mapping as an Unbiased Method for Identifying Molecular Pathways and Processes Affected by Toxicant Exposure: Application to Acute Effects Caused by the Rodent Non-Genotoxic Carcinogen Diethylhexylphthalate Toxicol. Sci., August 1, 2005; 86(2): 453 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Li, N. Gokden, M. D. Okusa, R. Bhatt, and D. Portilla Anti-inflammatory effect of fibrate protects from cisplatin-induced ARF Am J Physiol Renal Physiol, August 1, 2005; 289(2): F469 - F480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mouthiers, A. Baillet, C. Delomenie, D. Porquet, and N. Mejdoubi-Charef Peroxisome Proliferator-Activated Receptor {alpha} Physically Interacts with CCAAT/Enhancer Binding Protein (C/EBP{beta}) to Inhibit C/EBP{beta}-Responsive {alpha}1-Acid Glycoprotein Gene Expression Mol. Endocrinol., May 1, 2005; 19(5): 1135 - 1146. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Verschuur, M. de Jong, L. Felida, M. P. M. de Maat, and H. L. Vos A Hepatocyte Nuclear Factor-3 Site in the Fibrinogen {beta} Promoter Is Important for Interleukin 6-induced Expression, and Its Activity Is Influenced by the Adjacent -148C/T Polymorphism J. Biol. Chem., April 29, 2005; 280(17): 16763 - 16771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Vanschoonbeek, M. A.H. Feijge, M. Paquay, J. Rosing, W. Saris, C. Kluft, P. L.A. Giesen, M. P.M. de Maat, and J. W.M. Heemskerk Variable Hypocoagulant Effect of Fish Oil Intake in Humans: Modulation of Fibrinogen Level and Thrombin Generation Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1734 - 1740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Blanquart, R. Mansouri, R. Paumelle, J.-C. Fruchart, B. Staels, and C. Glineur The Protein Kinase C Signaling Pathway Regulates a Molecular Switch between Transactivation and Transrepression Activity of the Peroxisome Proliferator-Activated Receptor {alpha} Mol. Endocrinol., August 1, 2004; 18(8): 1906 - 1918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-h. Shih, S.-L. Chen, C.-C. Yen, Y.-H. Huang, C.-d. Chen, Y.-S. Lee, and K.-h. Lin Thyroid Hormone Receptor-Dependent Transcriptional Regulation of Fibrinogen and Coagulation Proteins Endocrinology, June 1, 2004; 145(6): 2804 - 2814. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Gervois, R. Kleemann, A. Pilon, F. Percevault, W. Koenig, B. Staels, and T. Kooistra Global Suppression of IL-6-induced Acute Phase Response Gene Expression after Chronic in Vivo Treatment with the Peroxisome Proliferator-activated Receptor-{alpha} Activator Fenofibrate J. Biol. Chem., April 16, 2004; 279(16): 16154 - 16160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Tsimihodimos, A. Kostoula, A. Kakafika, E. Bairaktari, A. D. Tselepis, D. P. Mikhailidis, and M. Elisaf Effect of Fenofibrate on Serum Inflammatory Markers in Patients With High Triglyceride Values Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2004; 9(1): 27 - 33. [Abstract] [PDF]
|
|
|
|
|
|
M. P. Holland, S. P. Bliss, K. A. Berghorn, and M. S. Roberson A Role for CCAAT/Enhancer-Binding Protein {beta} in the Basal Regulation of the Distal-Less 3 Gene Promoter in Placental Cells Endocrinology, March 1, 2004; 145(3): 1096 - 1105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Meissner, M. Stein, C. Urbich, K. Reisinger, G. Suske, B. Staels, R. Kaufmann, and J. Gille PPAR{alpha} Activators Inhibit Vascular Endothelial Growth Factor Receptor-2 Expression by Repressing Sp1-Dependent DNA Binding and Transactivation Circ. Res., February 20, 2004; 94(3): 324 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kleemann, P. P. Gervois, L. Verschuren, B. Staels, H. M. G. Princen, and T. Kooistra Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFkappa B-C/EBP-beta complex formation Blood, January 15, 2003; 101(2): 545 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Duez, Y.-S. Chao, M. Hernandez, G. Torpier, P. Poulain, S. Mundt, Z. Mallat, E. Teissier, C. A. Burton, A. Tedgui, et al. Reduction of Atherosclerosis by the Peroxisome Proliferator-activated Receptor alpha Agonist Fenofibrate in Mice J. Biol. Chem., December 6, 2002; 277(50): 48051 - 48057. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kluft, R. Kleemann, and M.P.M. de Maat How best to counteract the enemies? By controlling inflammation in the coronary circulation Eur. Heart J. Suppl., November 1, 2002; 4(suppl_G): G53 - G65. [Abstract] [PDF]
|
|
|
|
|
|
G. Min, J. K. Kemper, and B. Kemper Glucocorticoid Receptor-interacting Protein 1 Mediates Ligand-independent Nuclear Translocation and Activation of Constitutive Androstane Receptor in Vivo J. Biol. Chem., July 12, 2002; 277(29): 26356 - 26363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. BOCHER, I. PINEDA-TORRA, J.-C. FRUCHART, and B. STAELS PPARs: Transcription Factors Controlling Lipid and Lipoprotein Metabolism Ann. N.Y. Acad. Sci., June 1, 2002; 967(1): 7 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Barbier, I. P. Torra, Y. Duguay, C. Blanquart, J.-C. Fruchart, C. Glineur, and B. Staels Pleiotropic Actions of Peroxisome Proliferator-Activated Receptors in Lipid Metabolism and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., May 1, 2002; 22(5): 717 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Molavi, N. Rasouli, and J. L. Mehta Peroxisome Proliferator-Activated Receptor Ligands as Antiatherogenic Agents: Panacea or Another Pandora's Box? Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2002; 7(1): 1 - 8. [Abstract] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
