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 Ray, D. M.
Right arrow Articles by Phipps, R. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ray, D. M.
Right arrow Articles by Phipps, R. P.
The Journal of Immunology, 2005, 174: 4060-4069.
Copyright © 2005 by The American Association of Immunologists

CD40 Engagement Prevents Peroxisome Proliferator-Activated Receptor {gamma} Agonist-Induced Apoptosis of B Lymphocytes and B Lymphoma Cells by an NF-{kappa}B-Dependent Mechanism1

Denise M. Ray*, Filiz Akbiyik*,{ddagger}, Steven H. Bernstein{dagger} and Richard P. Phipps2,*

* Departments of Environmental Medicine, and Microbiology and Immunology, The Lung Biology and Disease Program, University of Rochester Medical Center, School of Medicine and Dentistry, {dagger} Lymphoma Biology Program, James P. Wilmot Cancer Center, Rochester, NY 14642; and {ddagger} Department of Biochemistry, Hacettepe University, Ankara, Turkey

Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) is a transcription factor important in fat metabolism and is emerging as an important regulator of immunity and inflammation. We previously demonstrated that normal and malignant B lineage cells express PPAR{gamma} and die by apoptosis after PPAR{gamma} agonist exposure. In this study, we used the WEHI-231 mouse B lymphoma and normal mouse spleen B lymphocytes to elucidate the mechanism of PPAR{gamma} agonist-induced apoptosis, and to determine whether an apoptosis rescue mechanism exists. In WEHI-231 cells, the natural PPAR{gamma} agonist 15-deoxy-{Delta}12,14-PGJ2 and the synthetic PPAR{gamma} agonist ciglitazone induced activation of caspase 3 and caspase 9, a decrease in mitochondrial membrane potential, and caused cleavage of the caspase substrate poly(ADP-ribose) polymerase. We next tested whether CD40, whose engagement delivers a potent prosurvival signal for B cells, could protect B cells from PPAR{gamma} agonist-induced apoptosis. CD40 engagement with CD40L significantly blunted the ability of PPAR{gamma} agonists to induce apoptosis of B lymphocytes and prevented the inhibition of NF-{kappa}B mobilization by 15-deoxy-{Delta}12,14-PGJ2 and ciglitazone. Interestingly, PPAR{gamma} agonists induced an increase in I{kappa}B{alpha} and I{kappa}B{beta} protein levels, which was prevented with CD40 engagement. The rescue mechanism induced by CD40 engagement was dependent on NF-{kappa}B, as an NF-{kappa}B inhibitor prevented rescue. Apoptosis induction by PPAR{gamma} ligands may be important for immune regulation by killing B lymphocytes as a rapid means to dampen inflammation. Moreover, the ability of PPAR{gamma} agonists to kill malignant B lineage cells has implications for their use as anti-B lymphoma agents.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
S. L. Bissonnette, J. E. Teague, D. H. Sherr, and J. J. Schlezinger
An Endogenous Prostaglandin Enhances Environmental Phthalate-Induced Apoptosis in Bone Marrow B Cells: Activation of Distinct but Overlapping Pathways
J. Immunol., August 1, 2008; 181(3): 1728 - 1736.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. E. Milam, V. G. Keshamouni, S. H. Phan, B. Hu, S. R. Gangireddy, C. M. Hogaboam, T. J. Standiford, V. J. Thannickal, and R. C. Reddy
PPAR-{gamma} agonists inhibit profibrotic phenotypes in human lung fibroblasts and bleomycin-induced pulmonary fibrosis
Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L891 - L901.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
J. J. Schlezinger, J. K. Emberley, S. L. Bissonnette, and D. H. Sherr
An L-Tyrosine Derivative and PPAR{gamma} Agonist, GW7845, Activates a Multifaceted Caspase Cascade in Bone Marrow B Cells
Toxicol. Sci., July 1, 2007; 98(1): 125 - 136.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. A. Wohlfert, F. C. Nichols, E. Nevius, and R. B. Clark
Peroxisome Proliferator-Activated Receptor {gamma} (PPAR{gamma}) and Immunoregulation: Enhancement of Regulatory T Cells through PPAR{gamma}-Dependent and -Independent Mechanisms
J. Immunol., April 1, 2007; 178(7): 4129 - 4135.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Z. Sui, L. F. Sniderhan, G. Schifitto, R. P. Phipps, H. A. Gelbard, S. Dewhurst, and S. B. Maggirwar
Functional Synergy between CD40 Ligand and HIV-1 Tat Contributes to Inflammation: Implications in HIV Type 1 Dementia
J. Immunol., March 1, 2007; 178(5): 3226 - 3236.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. S. Brookes, K. Morse, D. Ray, A. Tompkins, S. M. Young, S. Hilchey, S. Salim, M. Konopleva, M. Andreeff, R. Phipps, et al.
The Triterpenoid 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic Acid and Its Derivatives Elicit Human Lymphoid Cell Apoptosis through a Novel Pathway Involving the Unregulated Mitochondrial Permeability Transition Pore
Cancer Res., February 15, 2007; 67(4): 1793 - 1802.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. M. Ray, F. Akbiyik, and R. P. Phipps
The Peroxisome Proliferator-Activated Receptor {gamma} (PPAR{gamma}) Ligands 15-Deoxy-{Delta}12,14-Prostaglandin J2 and Ciglitazone Induce Human B Lymphocyte and B Cell Lymphoma Apoptosis by PPAR{gamma}-Independent Mechanisms
J. Immunol., October 15, 2006; 177(8): 5068 - 5076.
[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
 CarcinogenesisHome page
S. S. Wang, S. Davis, J. R. Cerhan, P. Hartge, R. K. Severson, W. Cozen, Q. Lan, R. Welch, S. J. Chanock, and N. Rothman
Polymorphisms in oxidative stress genes and risk for non-Hodgkin lymphoma
Carcinogenesis, September 1, 2006; 27(9): 1828 - 1834.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
F. E. Turner, S. Broad, F. L. Khanim, A. Jeanes, S. Talma, S. Hughes, C. Tselepis, and N. A. Hotchin
Slug Regulates Integrin Expression and Cell Proliferation in Human Epidermal Keratinocytes
J. Biol. Chem., July 28, 2006; 281(30): 21321 - 21331.
[Abstract] [Full Text] [PDF]

Home page
 ASH ANNUAL MEETING ABSTRACTSHome page
D. Ray, K. Morse, S. Hilchey, T. Garcia, R. Felgar, S. Maggirwar, R. Phipps, and S. H. Bernstein
The Novel Triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic Acid (CDDO) Induces Apoptosis of Human Diffuse Large B-Cell Lymphoma Cells (DLCL) through a Peroxisome Proliferator-Activated Receptor {gamma} (PPAR{gamma}) Independent Pathway Which Is Enhanced by NF{kappa}B Inhibition.
Blood (ASH Annual Meeting Abstracts), November 16, 2005; 106(11): 2425 - 2425.
[Abstract]

Home page
 IOVSHome page
S. E. Feldon, D. J. J. Park, C. W. O'Loughlin, V. T. Nguyen, S. Landskroner-Eiger, D. Chang, T. H. Thatcher, and R. P. Phipps
Autologous T-Lymphocytes Stimulate Proliferation of Orbital Fibroblasts Derived from Patients with Graves' Ophthalmopathy
Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 3913 - 3921.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2005 by The American Association of Immunologists, Inc. All rights reserved.