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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, C.-W.
Right arrow Articles by Lin, W.-W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, C.-W.
Right arrow Articles by Lin, W.-W.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*ACETYLCYSTEINE
*L-TYROSINE
*NITRIC OXIDE
The Journal of Immunology, 2003, 171: 979-988.
Copyright © 2003 by The American Association of Immunologists

Inhibition of IFN-{gamma}-Mediated Inducible Nitric Oxide Synthase Induction by the Peroxisome Proliferator-Activated Receptor {gamma} Agonist, 15-Deoxy-{Delta}12,14-Prostaglandin J2, Involves Inhibition of the Upstream Janus Kinase/STAT1 Signaling Pathway1

Ching-Wen Chen, Ying-Hsin Chang, Chin-Ju Tsi and Wan-Wan Lin2

Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan

Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) ligands have been reported to exert anti-inflammatory activities in macrophages by competition for transcriptional coactivators with some transcriptional factors, including NF-{kappa}B. In the present study the influence of PPAR{gamma} activators on IFN-{gamma}-elicited macrophage stimulation and signaling cascades was investigated. The results show that IFN-{gamma}-induced inducible NO synthase (iNOS) gene transcription, iNOS protein induction, and NO production are more sensitive to inhibition by 15-deoxy-{Delta}12,14-prostaglandin J2 (15dPGJ2) than by the other two PPAR{gamma} agonists, GW1929 and ciglitazone. Delayed addition of 15dPGJ2 for 2 h resulted in reduced inhibition, suggesting action by 15dPGJ2 on the upstream signaling cascades. Immunoblotting, DNA binding, and reporter gene assays consistently revealed the inhibitory ability of 15dPGJ2, but not GW1929 or ciglitazone, on IFN-{gamma}-elicited signaling cascades, including tyrosine phosphorylation of Janus tyrosine protein kinase 2 and STAT1, DNA binding, and IFN regulatory factor-1 trans-activation of STAT1. These effects of 15dPGJ2 were not abrogated by the PPAR{gamma} antagonist, bisphenol A diglycidyl ether, indicating the PPAR{gamma}-independent actions. 15dPGJ2 also attenuated IL-6-induced tyrosine phosphorylation of STAT1 and STAT3 in Hep3B hepatoma cells. Consistent with the inhibitory effect of reactive oxygen species on STAT1 signaling, STAT1 inhibition by 15dPGJ2 was abrogated by N-acetylcysteine, glutathione, superoxide dismutase, and catalase. Furthermore, 15dPGJ2-induced inhibition of STAT1 phosphorylation and NO production still occurred in the presence of peroxovanadate, ruling out the action mechanism of 15dPGJ2 on tyrosine phosphatase. Taken together, for the first time in this study we demonstrate that 15dPGJ2 can inhibit cytokine-stimulated Janus kinase 2-STAT signaling through a PPAR{gamma}-independent, reactive oxygen species-dependent mechanism. These data provide a novel molecular mechanism of iNOS inhibition by 15dPGJ2 and confirm its physiological role in anti-inflammation.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
T. Ichikawa, J. Zhang, K. Chen, Y. Liu, F. J. Schopfer, P. R. S. Baker, B. A. Freeman, Y. E. Chen, and T. Cui
Nitroalkenes Suppress Lipopolysaccharide-Induced Signal Transducer and Activator of Transcription Signaling in Macrophages: A Critical Role of Mitogen-Activated Protein Kinase Phosphatase 1
Endocrinology, August 1, 2008; 149(8): 4086 - 4094.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
U. Panzer, G. Zahner, U. Wienberg, O. M. Steinmetz, A. Peters, J.-E. Turner, H.-J. Paust, G. Wolf, R. A. K. Stahl, and A. Schneider
15-Deoxy-{Delta}12,14-prostaglandin J2 inhibits INF-{gamma}-induced JAK/STAT1 signalling pathway activation and IP-10/CXCL10 expression in mesangial cells
Nephrol. Dial. Transplant., July 2, 2008; (2008) gfn361v1.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. Linard, O. Gremy, and M. Benderitter
Reduction of Peroxisome Proliferation-Activated Receptor {gamma} Expression by {gamma}-Irradiation as a Mechanism Contributing to Inflammatory Response in Rat Colon: Modulation by the 5-Aminosalicylic Acid Agonist
J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 911 - 920.
[Abstract] [Full Text] [PDF]

Home page
 J BiochemHome page
N. Nagai, Y. Ito, and H. Okamura
Involvement of Interleukin 18 in Cataract Development in Hereditary Cataract UPL Rats
J. Biochem., November 1, 2007; 142(5): 597 - 603.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
M. Stoltz, C. Ahlm, A. Lundkvist, and J. Klingstrom
Lambda Interferon (IFN-{lambda}) in Serum Is Decreased in Hantavirus-Infected Patients, and In Vitro-Established Infection Is Insensitive to Treatment with All IFNs and Inhibits IFN-{gamma}-Induced Nitric Oxide Production
J. Virol., August 15, 2007; 81(16): 8685 - 8691.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. S. Kristof, J. Fielhaber, A. Triantafillopoulos, S. Nemoto, and J. Moss
Phosphatidylinositol 3-Kinase-dependent Suppression of the Human Inducible Nitric-oxide Synthase Promoter Is Mediated by FKHRL1
J. Biol. Chem., August 18, 2006; 281(33): 23958 - 23968.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Akasaki, G. Liu, H. H. Matundan, H. Ng, X. Yuan, Z. Zeng, K. L. Black, and J. S. Yu
A Peroxisome Proliferator-activated Receptor-{gamma} Agonist, Troglitazone, Facilitates Caspase-8 and -9 Activities by Increasing the Enzymatic Activity of Protein-tyrosine Phosphatase-1B on Human Glioma Cells
J. Biol. Chem., March 10, 2006; 281(10): 6165 - 6174.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Han, J. D. Ritzenthaler, H. N. Rivera, and J. Roman
Peroxisome proliferator-activated receptor-{gamma} ligands suppress fibronectin gene expression in human lung carcinoma cells: involvement of both CRE and Sp1
Am J Physiol Lung Cell Mol Physiol, September 1, 2005; 289(3): L419 - L428.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
J. D. Ji, H. J. Kim, Y. H. Rho, S. J. Choi, Y. H. Lee, H. J. Cheon, J. Sohn, and G. G. Song
Inhibition of IL-10-induced STAT3 activation by 15-deoxy-{Delta}12,14-prostaglandin J2
Rheumatology, August 1, 2005; 44(8): 983 - 988.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S. Han, H. N. Rivera, and J. Roman
Peroxisome Proliferator-Activated Receptor-{gamma} Ligands Inhibit {alpha}5 Integrin Gene Transcription in Non-Small Cell Lung Carcinoma Cells
Am. J. Respir. Cell Mol. Biol., April 1, 2005; 32(4): 350 - 359.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
F. J. Sanchez-Gomez, E. Cernuda-Morollon, K. Stamatakis, and D. Perez-Sala
Protein Thiol Modification by 15-deoxy-{Delta}12,14-Prostaglandin J2 Addition in Mesangial Cells: Role in the Inhibition of Pro-inflammatory Genes
Mol. Pharmacol., November 1, 2004; 66(5): 1349 - 1358.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2003 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2003 by The American Association of Immunologists, Inc. All rights reserved.