The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ward, C.
Right arrow Articles by Rossi, A. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ward, C.
Right arrow Articles by Rossi, A. G.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*PROSTAGLANDIN F2ALPHA
The Journal of Immunology, 2002, 168: 6232-6243.
Copyright © 2002 by The American Association of Immunologists

Prostaglandin D2 and Its Metabolites Induce Caspase-Dependent Granulocyte Apoptosis That Is Mediated Via Inhibition of I{kappa}B{alpha} Degradation Using a Peroxisome Proliferator-Activated Receptor-{gamma}-Independent Mechanism1

Carol Ward*, Ian Dransfield*, Joanna Murray*, Stuart N. Farrow{dagger}, Christopher Haslett* and Adriano G. Rossi2,*

* Rayne Laboratory, Respiratory Medicine Unit, Medical Research Council Center for Inflammation Research, University of Edinburgh Medical School, Edinburgh, United Kingdom; and {dagger} Cell Biology Unit, GlaxoSmithKline, Stevenage, United Kingdom

Many inflammatory mediators retard granulocyte apoptosis. Most natural PGs studied herein (e.g., PGE2, PGA2, PGA1, PGF2{alpha}) either delayed apoptosis or had no effect, whereas PGD2 and its metabolite PGJ2 selectively induced eosinophil, but not neutrophil apoptosis. This novel proapoptotic effect does not appear to be mediated via classical PG receptor ligation or by elevation of intracellular cAMP or Ca2+. Intriguingly, the sequential metabolites {Delta}12PGJ2 and 15-deoxy-{Delta}12, {Delta}14-PGJ2 (15dPGJ2) induced caspase-dependent apoptosis in both granulocytes, an effect that did not involve de novo protein synthesis. Despite the fact that {Delta}12PGJ2 and 15dPGJ2 are peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) activators, apoptosis was not mimicked by synthetic PPAR-{gamma} and PPAR-{alpha} ligands or blocked by an irreversible PPAR-{gamma} antagonist. Furthermore, {Delta}12PGJ2 and 15dPGJ2 inhibited LPS-induced I{kappa}B{alpha} degradation and subsequent inhibition of neutrophil apoptosis, suggesting that apoptosis is mediated via PPAR-{gamma}-independent inhibition of NF-{kappa}B activation. In addition, we show that TNF-{alpha}-mediated loss of cytoplasmic I{kappa}B{alpha} in eosinophils is inhibited by 15dPGJ2 in a concentration-dependent manner. The selective induction of eosinophil apoptosis by PGD2 and PGJ2 may help define novel therapeutic pathways in diseases in which it would be desirable to specifically remove eosinophils but retain neutrophils for antibacterial host defense. The powerful proapoptotic effects of {Delta}12PGJ2 and 15dPGJ2 in both granulocyte types suggest that these natural products control the longevity of key inflammatory cells and may be relevant to understanding the control and resolution of inflammation.




This article has been cited by other articles:


Home page
 J Am Coll CardiolHome page
G. Orasanu, O. Ziouzenkova, P. R. Devchand, V. Nehra, O. Hamdy, E. S. Horton, and J. Plutzky
The Peroxisome Proliferator-Activated Receptor-{gamma} Agonist Pioglitazone Represses Inflammation in a Peroxisome Proliferator-Activated Receptor-{alpha}-Dependent Manner In Vitro and In Vivo in Mice
J. Am. Coll. Cardiol., September 2, 2008; 52(10): 869 - 881.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
H. Sandig, J. E. Pease, and I. Sabroe
Contrary prostaglandins: the opposing roles of PGD2 and its metabolites in leukocyte function
J. Leukoc. Biol., February 1, 2007; 81(2): 372 - 382.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S.-H. Jo, C. Yang, Q. Miao, M. Marzec, M. A. Wasik, P. Lu, and Y. L. Wang
Peroxisome Proliferator-Activated Receptor {gamma} Promotes Lymphocyte Survival through Its Actions on Cellular Metabolic Activities
J. Immunol., September 15, 2006; 177(6): 3737 - 3745.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
R. Soares, I. Azevedo, D. A. Sawatzky, and A. G. Rossi
Apigenin: Is It a Pro- or Anti-Inflammatory Agent?
Am. J. Pathol., May 1, 2006; 168(5): 1762 - 1763.
[Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
T.-N. Lin, W.-M. Cheung, J.-S. Wu, J.-J. Chen, H. Lin, J.-J. Chen, J.-Y. Liou, S.-K. Shyue, and K. K. Wu
15d-Prostaglandin J2 Protects Brain From Ischemia-Reperfusion Injury
Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 481 - 487.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
M. Soller, A. Tautenhahn, B. Brune, K. Zacharowski, S. John, H. Link, and A. von Knethen
Peroxisome proliferator-activated receptor {gamma} contributes to T lymphocyte apoptosis during sepsis
J. Leukoc. Biol., January 1, 2006; 79(1): 235 - 243.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Ear, A. Cloutier, and P. P. McDonald
Constitutive Nuclear Expression of the I{kappa}B Kinase Complex and Its Activation in Human Neutrophils
J. Immunol., August 1, 2005; 175(3): 1834 - 1842.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
W. Almishri, C. Cossette, J. Rokach, J. G. Martin, Q. Hamid, and W. S. Powell
Effects of Prostaglandin D2, 15-Deoxy-{Delta}12,14-prostaglandin J2, and Selective DP1 and DP2 Receptor Agonists on Pulmonary Infiltration of Eosinophils in Brown Norway Rats
J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 64 - 69.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
R. Piva, P. Gianferretti, A. Ciucci, R. Taulli, G. Belardo, and M. G. Santoro
15-Deoxy-{Delta}12,14-prostaglandin J2 induces apoptosis in human malignant B cells: an effect associated with inhibition of NF-{kappa}B activity and down-regulation of antiapoptotic proteins
Blood, February 15, 2005; 105(4): 1750 - 1758.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. A. Ruiz, S. C. Kim, R. B. Sartor, and D. Haller
15-Deoxy-{Delta}12,14-prostaglandin J2-mediated ERK Signaling Inhibits Gram-negative Bacteria-induced RelA Phosphorylation and Interleukin-6 Gene Expression in Intestinal Epithelial Cells through Modulation of Protein Phosphatase 2A Activity
J. Biol. Chem., August 20, 2004; 279(34): 36103 - 36111.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Alvarez-Maqueda, R. E. Bekay, G. Alba, J. Monteseirin, P. Chacon, A. Vega, J. Martin-Nieto, F. J. Bedoya, E. Pintado, and F. Sobrino
15-Deoxy-{Delta}12,14-prostaglandin J2 Induces Heme Oxygenase-1 Gene Expression in a Reactive Oxygen Species-dependent Manner in Human Lymphocytes
J. Biol. Chem., May 21, 2004; 279(21): 21929 - 21937.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Relic, V. Benoit, N. Franchimont, C. Ribbens, M.-J. Kaiser, P. Gillet, M.-P. Merville, V. Bours, and M. G. Malaise
15-Deoxy-{Delta}12,14-prostaglandin J2 Inhibits Bay 11-7085-induced Sustained Extracellular Signal-regulated Kinase Phosphorylation and Apoptosis in Human Articular Chondrocytes and Synovial Fibroblasts
J. Biol. Chem., May 21, 2004; 279(21): 22399 - 22403.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
K. S. Mix, C. I. Coon, E. D. Rosen, N. Suh, M. B. Sporn, and C. E. Brinckerhoff
Peroxisome Proliferator-Activated Receptor-{gamma}-Independent Repression of Collagenase Gene Expression by 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic Acid and Prostaglandin 15-Deoxy-{Delta}(12,14) J2: A Role for Smad Signaling
Mol. Pharmacol., February 1, 2004; 65(2): 309 - 318.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
J. F. Maddox, A. C. Domzalski, R. A. Roth, and P. E. Ganey
15-Deoxy Prostaglandin J2 Enhances Allyl Alcohol-Induced Toxicity in Rat Hepatocytes
Toxicol. Sci., February 1, 2004; 77(2): 290 - 298.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Kettritz, M. Choi, S. Rolle, M. Wellner, and F. C. Luft
Integrins and Cytokines Activate Nuclear Transcription Factor-{kappa}B in Human Neutrophils
J. Biol. Chem., January 23, 2004; 279(4): 2657 - 2665.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. N. Hata, R. Zent, M. D. Breyer, and R. M. Breyer
Expression and Molecular Pharmacology of the Mouse CRTH2 Receptor
J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 463 - 470.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
J. R. Brown, D. Goldblatt, J. Buddle, L. Morton, and A. J. Thrasher
Diminished production of anti-inflammatory mediators during neutrophil apoptosis and macrophage phagocytosis in chronic granulomatous disease (CGD)
J. Leukoc. Biol., May 1, 2003; 73(5): 591 - 599.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
A. Tautenhahn, B. Brune, and A. von Knethen
Activation-induced PPAR{gamma} expression sensitizes primary human T cells toward apoptosis
J. Leukoc. Biol., May 1, 2003; 73(5): 665 - 672.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
K. M. Jung, K. S. Park, J. H. Oh, S. Y. Jung, K. H. Yang, Y. S. Song, D. J. Son, Y. H. Park, Y. P. Yun, M. K. Lee, et al.
Activation of p38 Mitogen-Activated Protein Kinase and Activator Protein-1 during the Promotion of Neurite Extension of PC-12 Cells by 15-Deoxy-Delta 12,14-prostaglandin J2
Mol. Pharmacol., March 1, 2003; 63(3): 607 - 616.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Li, Y. Yang, and R. L. Stevens
RasGRP4 Regulates the Expression of Prostaglandin D2 in Human and Rat Mast Cell Lines
J. Biol. Chem., February 7, 2003; 278(7): 4725 - 4729.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.