JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
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 Yamazaki, R.
Right arrow Articles by Kawai, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yamazaki, R.
Right arrow Articles by Kawai, S.

Vol. 302, Issue 1, 18-25, July 2002

Nonsteroidal Anti-Inflammatory Drugs Induce Apoptosis in Association with Activation of Peroxisome Proliferator-Activated Receptor gamma  in Rheumatoid Synovial Cells

Ryuta Yamazaki , Natsuko Kusunoki, Takeshi Matsuzaki, Shusuke Hashimoto and Shinichi Kawai

Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan (R.Y., N.K., S.K.); and Yakult Central Institute for Microbiological Research, Tokyo, Japan (R.Y., T.M., S.H.)

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce apoptosis in a variety of cell lines. In this study, we examined the effect of NSAIDs on the growth and apoptosis of synovial cells from patients with rheumatoid arthritis and analyzed the activation of peroxisome proliferator-activated receptor gamma  (PPARgamma ) as a possible mechanism of action of NSAIDs. Cell proliferation and viability were assessed from 5-bromo-2'-deoxyuridine incorporation and by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay, respectively. The apoptosis of synovial cells was identified by DNA fragmentation assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Indometacin, diclofenac, oxaprozin, and zaltoprofen reduced cell proliferation and induced apoptotic cell death in synovial cells, whereas ketoprofen and acetaminophen did not. N-[2-(cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide (NS-398), a selective cyclooxygenase-2 inhibitor, also inhibited cell proliferation, whereas it did not cause apoptosis. Rheumatoid synovial cells expressed PPARgamma mRNA, and the PPARgamma ligands 15-deoxy-Delta 12,14-prostaglandin J2 and troglitazone reduced the proliferation and induced apoptosis in synovial cells. Luciferase reporter assay demonstrated that not only PPARgamma ligands but also NSAIDs, which could induce apoptosis, increased the activation of PPARgamma in synovial cells. Furthermore, the ability of NSAIDs and PPARgamma ligands to stimulate the activation of PPARgamma correlated with their ability to decrease cell viability(r = 0.92, p < 0.01) and ability to induce DNA fragmentation (r = 0.97, p < 0.001) in synovial cells. These results suggest that PPARgamma is an attractive target for induction of apoptosis in rheumatoid synovial cells and that the activation of the PPARgamma pathway is associated with the apoptotic action of NSAIDs.

0022-3565/02/3021-0018$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J Biomol ScreenHome page
T. Haupl, M. Yahyawi, C. Lubke, J. Ringe, T. Rohrlach, G. R. Burmester, M. Sittinger, and C. Kaps
Gene Expression Profiling of Rheumatoid Arthritis Synovial Cells Treated with Antirheumatic Drugs
J Biomol Screen, April 1, 2007; 12(3): 328 - 340.
[Abstract] [PDF]

Home page
 Rheumatology (Oxford)Home page
S. Lev-Ari, L. Strier, D. Kazanov, O. Elkayam, D. Lichtenberg, D. Caspi, and N. Arber
Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells
Rheumatology, February 1, 2006; 45(2): 171 - 177.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. Lev-Ari, L. Strier, D. Kazanov, L. Madar-Shapiro, H. Dvory-Sobol, I. Pinchuk, B. Marian, D. Lichtenberg, and N. Arber
Celecoxib and Curcumin Synergistically Inhibit the Growth of Colorectal Cancer Cells
Clin. Cancer Res., September 15, 2005; 11(18): 6738 - 6744.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
N. Morioka, K. Kumagai, K. Morita, S. Kitayama, and T. Dohi
Nonsteroidal Anti-Inflammatory Drugs Potentiate 1-Methyl-4-phenylpyridinium (MPP+)-Induced Cell Death by Promoting the Intracellular Accumulation of MPP+ in PC12 Cells
J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 800 - 807.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. L. Lovering, J. P. Ride, C. M. Bunce, J. C. Desmond, S. M. Cummings, and S. A. White
Crystal Structures of Prostaglandin D2 11-Ketoreductase (AKR1C3) in Complex with the Nonsteroidal Anti-Inflammatory Drugs Flufenamic Acid and Indomethacin
Cancer Res., March 1, 2004; 64(5): 1802 - 1810.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. Ando, Y. Murakami, F. Kojima, H. Endo, H. Kitasato, A. Hashimoto, H. Kobayashi, M. Majima, M. Inoue, H. Kondo, et al.
Retrovirally Introduced Prostaglandin D2 Synthase Suppresses Lung Injury Induced by Bleomycin
Am. J. Respir. Cell Mol. Biol., May 1, 2003; 28(5): 582 - 591.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
G. Hawcroft, S. H. Gardner, and M. A. Hull
Activation of Peroxisome Proliferator-Activated Receptor gamma Does Not Explain the Antiproliferative Activity of the Nonsteroidal Anti-Inflammatory Drug Indomethacin on Human Colorectal Cancer Cells
J. Pharmacol. Exp. Ther., May 1, 2003; 305(2): 632 - 637.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2002 by the American Society for Pharmacology and Experimental Therapeutics.