HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 51, 51340-51346, December 19, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/51/51340    most recent M310865200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Worley, J. R. Articles by Gavrilovic, J. Search for Related Content PubMed PubMed Citation Articles by Worley, J. R. Articles by Gavrilovic, J. Social Bookmarking                      What's this?

Metalloproteinase Expression in PMA-stimulated THP-1 Cells

EFFECTS OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR- (PPAR) AGONISTS AND 9-CIS-RETINOIC ACID^*

Joanna R. Worley, Mark D. Baugh¶, David A. Hughes||, Dylan R. Edwards, Aileen Hogan, Mike J. Sampson, and Jelena Gavrilovic**

From the School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, United Kingdom, the Bertram Diabetes Research Unit, Norfolk & Norwich University Hospital NHS Trust, Norwich NR4 7UY, United Kingdom, and the ^||Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, United Kingdom

The PPAR agonists, thiazolidinediones (TZDs), have anti-inflammatory properties as well as increasing insulin sensitivity. This has widened their therapeutic scope to treat inflammatory diseases such as atherosclerosis in addition to Type 2 Diabetes. TZDs are known to reduce monocyte/macrophage expression of Matrix metalloproteinase (MMP)-9, which is implicated in atherosclerotic plaque destabilization. This study aims to identify other metalloproteinase genes of the ADAM (A Disintegin And Metalloproteinase) and ADAMTS families that are regulated by PPAR or RXR agonists, which are potentially important in type 2 diabetes and/or related atherosclerosis. The synthetic PPAR agonist, GW7845, and the natural agonist 15d-PGJ₂, suppressed PMA stimulated MMP-9 in human monocyte-like cells (THP-1) only in the presence of 9-cis-retinoic acid. Quantitative Real-Time PCR showed that this reduction was regulated at the mRNA level. Expression of ADAMs 8, 9, and 17 were increased, and ADAM15 was decreased by stimulation of THP-1 with PMA, although these ADAMs were not regulated by PPAR or RXR agonists. PMA-induced ADAM28 expression was further enhanced by the addition of 9-cis-retinoic acid. ADAMTS4, implicated in rheumatoid arthritis, was expressed in THP-1 cells, and significantly increased after 24 h of PMA stimulation. ADAMTS4 expression was suppressed by both PPAR and RXR agonists and was undetectable when the agonists were combined. Pretreatment of THP-1 cells with the PPAR antagonist, GW9662, suggests that PPAR plays subtly different roles in the regulation of MMP-9, ADAMTS4 and ADAM28 gene expression. These results indicate that PPAR and RXR agonists have complex effects on monocyte metalloproteinase expression, which may have implications for therapeutic strategies.

Received for publication, October 2, 2003

^* This work was supported by the Norwich and Norfolk Diabetes Trust and the Biotechnology and Biological Sciences Research Council. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Current Address: Organon Laboratories, Newhouse, Motherwell, UK.

^** To whom correspondence should be addressed: School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, UK. Tel.: 44-0-1603-593816; Fax: 44-0-1603-592250; E-mail: j.gavrilovic{at}uea.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. Coppola, D. Marmolino, D. Lu, Q. Wang, M. Cnop, M. Rai, F. Acquaviva, S. Cocozza, M. Pandolfo, and D. H. Geschwind Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPAR{gamma} pathway as a therapeutic target in Friedreich's ataxia Hum. Mol. Genet., July 1, 2009; 18(13): 2452 - 2461. [Abstract] [Full Text] [PDF]

				A. Gaurnier-Hausser, V. L. Rothman, S. Dimitrov, and G. P. Tuszynski The Novel Angiogenic Inhibitor, Angiocidin, Induces Differentiation of Monocytes to Macrophages Cancer Res., July 15, 2008; 68(14): 5905 - 5914. [Abstract] [Full Text] [PDF]

				F. Zapata-Gonzalez, F. Rueda, J. Petriz, P. Domingo, F. Villarroya, A. de Madariaga, and J. C. Domingo 9-cis-Retinoic Acid (9cRA), a Retinoid X Receptor (RXR) Ligand, Exerts Immunosuppressive Effects on Dendritic Cells by RXR-Dependent Activation: Inhibition of Peroxisome Proliferator-Activated Receptor {gamma} Blocks Some of the 9cRA Activities, and Precludes Them to Mature Phenotype Development J. Immunol., May 15, 2007; 178(10): 6130 - 6139. [Abstract] [Full Text] [PDF]

				B. Santiago-Josefat, C. Esselens, J. J. Bech-Serra, and J. Arribas Post-transcriptional Up-regulation of ADAM17 upon Epidermal Growth Factor Receptor Activation and in Breast Tumors J. Biol. Chem., March 16, 2007; 282(11): 8325 - 8331. [Abstract] [Full Text] [PDF]

				H. Sawai, J. Liu, H. A. Reber, O. J. Hines, and G. Eibl Activation of Peroxisome Proliferator-Activated Receptor-{gamma} Decreases Pancreatic Cancer Cell Invasion through Modulation of the Plasminogen Activator System Mol. Cancer Res., March 1, 2006; 4(3): 159 - 167. [Abstract] [Full Text] [PDF]

				S Soumian, R Gibbs, A Davies, and C Albrecht mRNA expression of genes involved in lipid efflux and matrix degradation in occlusive and ectatic atherosclerotic disease J. Clin. Pathol., December 1, 2005; 58(12): 1255 - 1260. [Abstract] [Full Text] [PDF]

				R. J.R. Singh, J. C. Mason, E. A. Lidington, D. R. Edwards, R. K. Nuttall, R. Khokha, V. Knauper, G. Murphy, and J. Gavrilovic Cytokine stimulated vascular cell adhesion molecule-1 (VCAM-1) ectodomain release is regulated by TIMP-3 Cardiovasc Res, July 1, 2005; 67(1): 39 - 49. [Abstract] [Full Text] [PDF]

				P. Stawowy, H. Meyborg, D. Stibenz, N. B. P. Stawowy, M. Roser, U. Thanabalasingam, J. P. Veinot, M. Chretien, N. G. Seidah, E. Fleck, et al. Furin-Like Proprotein Convertases Are Central Regulators of the Membrane Type Matrix Metalloproteinase-Pro-Matrix Metalloproteinase-2 Proteolytic Cascade in Atherosclerosis Circulation, May 31, 2005; 111(21): 2820 - 2827. [Abstract] [Full Text] [PDF]

				M. Francois, P. Richette, L. Tsagris, M. Raymondjean, M.-C. Fulchignoni-Lataud, C. Forest, J.-F. Savouret, and M.-T. Corvol Peroxisome Proliferator-activated Receptor-{gamma} Down-regulates Chondrocyte Matrix Metalloproteinase-1 via a Novel Composite Element J. Biol. Chem., July 2, 2004; 279(27): 28411 - 28418. [Abstract] [Full Text] [PDF]