Advertisement
JBC

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


     

Originally published In Press as doi:10.1074/jbc.M201207200 on May 22, 2002

J. Biol. Chem., Vol. 277, Issue 30, 27169-27175, July 26, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
277/30/27169    most recent
M201207200v1
Right arrow Submit a Letter to Editor
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 Email this article to a friend
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 arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wurster, A. L.
Right arrow Articles by Grusby, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wurster, A. L.
Right arrow Articles by Grusby, M. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Interleukin-4-mediated Protection of Primary B Cells from Apoptosis through Stat6-dependent Up-regulation of Bcl-xL*

Andrea L. WursterDagger , Vikki L. RodgersDagger , Morris F. White§, Thomas L. Rothstein, and Michael J. GrusbyDagger ||**

From the Dagger  Department of Immunology and Infectious Diseases, Harvard School of Public Health and § Howard Hughes Medical Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02115,  Departments of Medicine and Microbiology and the Evans Memorial Department of Clinical Research, Boston University Medical Center, Boston, Massachusetts 02118, and || Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Apoptosis is an integral aspect of B lymphocyte development and homeostasis and is regulated by the engagement of antigen costimulatory and cytokine receptors. Although it is well established that interleukin 4 (IL-4) is a potent anti-apoptotic cytokine for B lymphocytes, little is known about the IL-4-induced molecular events regulating cell survival. Stat6 is rapidly activated after IL-4 stimulation, but its role in B lymphocyte apoptosis has not been explored. In this report we demonstrate that Stat6 is a critical signaling molecule for IL-4 in protecting primary B cells from passive and Fas-induced cell death. We show that expression of the Bcl-2 family member, Bcl-xL, is induced maximally by IL-4 and anti-IgM/IL-4 in a Stat6-dependent manner. Additionally, we demonstrate that bcl-xL transcription is likely to be directly activated through a Stat6 binding site in the bcl-xL-flanking region. Finally, reconstitution of Stat6-deficient splenic B cells with Bcl-xL was able to protect those cells from Fas-induced cell death. These results suggest that the anti-apoptotic activity of IL-4 in B cells is mediated through the activation of Stat6 and subsequent transcription of Bcl-xL.

* This work was supported by National Institutes of Health Grants AI40171 (to M. J. G.) and AI40181 (to T. L. R.) and by the Mathers Foundation (to M. J. G.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

** A scholar of the Leukemia and Lymphoma Society. To whom correspondence should be addressed. Tel.: 617-432-1240; Fax: 617-432-0084; E-mail: mgrusby@hsph.harvard.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 BloodHome page
S. H. Cho, S. Goenka, T. Henttinen, P. Gudapati, A. Reinikainen, C. M. Eischen, R. Lahesmaa, and M. Boothby
PARP-14, a member of the B aggressive lymphoma family, transduces survival signals in primary B cells
Blood, March 12, 2009; 113(11): 2416 - 2425.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. Tahvanainen, T. Kallonen, H. Lahteenmaki, K. M. Heiskanen, J. Westermarck, K. V. S. Rao, and R. Lahesmaa
PRELI is a mitochondrial regulator of human primary T-helper cell apoptosis, STAT6, and Th2-cell differentiation
Blood, February 5, 2009; 113(6): 1268 - 1277.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. Buglio, G. V. Georgakis, S. Hanabuchi, K. Arima, N. M. Khaskhely, Y.-J. Liu, and A. Younes
Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines
Blood, August 15, 2008; 112(4): 1424 - 1433.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
F. J. Dufort, B. F. Bleiman, M. R. Gumina, D. Blair, D. J. Wagner, M. F. Roberts, Y. Abu-Amer, and T. C. Chiles
Cutting Edge: IL-4-Mediated Protection of Primary B Lymphocytes from Apoptosis via Stat6-Dependent Regulation of Glycolytic Metabolism
J. Immunol., October 15, 2007; 179(8): 4953 - 4957.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
A. Acacia de Sa Pinheiro, A. Morrot, S. Chakravarty, M. Overstreet, J. H. Bream, P. M. Irusta, and F. Zavala
IL-4 induces a wide-spectrum intracellular signaling cascade in CD8+ T cells
J. Leukoc. Biol., April 1, 2007; 81(4): 1102 - 1110.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
E. D. Hawkins, M. L. Turner, M. R. Dowling, C. van Gend, and P. D. Hodgkin
A model of immune regulation as a consequence of randomized lymphocyte division and death times
PNAS, March 20, 2007; 104(12): 5032 - 5037.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
K. J. Rautajoki, E. M. Marttila, T. A. Nyman, and R. Lahesmaa
Interleukin-4 Inhibits Caspase-3 by Regulating Several Proteins in the Fas Pathway during Initial Stages of Human T Helper 2 Cell Differentiation
Mol. Cell. Proteomics, February 1, 2007; 6(2): 238 - 251.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
H. Jin and T. R. Malek
Redundant and unique regulation of activated mouse B lymphocytes by IL-4 and IL-21
J. Leukoc. Biol., December 1, 2006; 80(6): 1416 - 1423.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. R. Herrin and L. B. Justement
Expression of the Adaptor Protein Hematopoietic Src Homology 2 is Up-Regulated in Response to Stimuli That Promote Survival and Differentiation of B Cells
J. Immunol., April 1, 2006; 176(7): 4163 - 4172.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Todaro, M. Zerilli, L. Ricci-Vitiani, M. Bini, M. Perez Alea, A. Maria Florena, L. Miceli, G. Condorelli, S. Bonventre, G. Di Gesu, et al.
Autocrine Production of Interleukin-4 and Interleukin-10 Is Required for Survival and Growth of Thyroid Cancer Cells
Cancer Res., February 1, 2006; 66(3): 1491 - 1499.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. Bilancio, K. Okkenhaug, M. Camps, J. L. Emery, T. Ruckle, C. Rommel, and B. Vanhaesebroeck
Key role of the p110{delta} isoform of PI3K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with p110{delta} function in B cells
Blood, January 15, 2006; 107(2): 642 - 650.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
A. Kelly-Welch, E. M. Hanson, and A. D. Keegan
Interleukin-4 (IL-4) Pathway
Sci. Signal., July 19, 2005; 2005(293): cm9 - cm9.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
S. Hussain, K. V. Salojin, and T. L. Delovitch
Hyperresponsiveness, Resistance to B-Cell Receptor--Dependent Activation-Induced Cell Death, and Accumulation of Hyperactivated B-Cells in Islets Is Associated With the Onset of Insulitis but not Type 1 Diabetes
Diabetes, August 1, 2004; 53(8): 2003 - 2011.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
M. Lohoff, H.-W. Mittrucker, A. Brustle, F. Sommer, B. Casper, M. Huber, D. A. Ferrick, G. S. Duncan, and T. W. Mak
Enhanced TCR-induced Apoptosis in Interferon Regulatory Factor 4-deficient CD4+ Th Cells
J. Exp. Med., July 19, 2004; 200(2): 247 - 253.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. E. Kelly-Welch, H. Y. Wang, L.-M. Wang, J. H. Pierce, G. Jay, F. Finkelman, and A. D. Keegan
Transgenic Expression of Insulin Receptor Substrate 2 in Murine B Cells Alters the Cell Density-Dependence of IgE Production In Vitro and Enhances IgE Production In Vivo
J. Immunol., March 1, 2004; 172(5): 2803 - 2810.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. E. Marra, Z. X. Zhang, B. Joe, J. Campbell, G. A. Levy, J. Penninger, and L. Zhang
IL-10 Induces Regulatory T Cell Apoptosis by Up-Regulation of the Membrane Form of TNF-{alpha}
J. Immunol., January 15, 2004; 172(2): 1028 - 1035.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
W.-L. Zhao, M. E. Daneshpouy, N. Mounier, J. Briere, C. Leboeuf, L.-F. Plassa, E. Turpin, J.-M. Cayuela, J.-C. Ameisen, C. Gisselbrecht, et al.
Prognostic significance of bcl-xL gene expression and apoptotic cell counts in follicular lymphoma
Blood, January 15, 2004; 103(2): 695 - 697.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
E. V. Acosta-Rodriguez, C. L. Montes, C. C. Motran, E. I. Zuniga, F.-T. Liu, G. A. Rabinovich, and A. Gruppi
Galectin-3 Mediates IL-4-Induced Survival and Differentiation of B Cells: Functional Cross-Talk and Implications during Trypanosoma cruzi Infection
J. Immunol., January 1, 2004; 172(1): 493 - 502.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Stassi, M. Todaro, M. Zerilli, L. Ricci-Vitiani, D. Di Liberto, M. Patti, A. Florena, F. Di Gaudio, G. Di Gesu, and R. De Maria
Thyroid Cancer Resistance to Chemotherapeutic Drugs via Autocrine Production of Interleukin-4 and Interleukin-10
Cancer Res., October 15, 2003; 63(20): 6784 - 6790.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. W. Wynes and D. W. H. Riches
Induction of Macrophage Insulin-Like Growth Factor-I Expression by the Th2 Cytokines IL-4 and IL-13
J. Immunol., October 1, 2003; 171(7): 3550 - 3559.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A. E. Kelly-Welch, E. M. Hanson, M. R. Boothby, and A. D. Keegan
Interleukin-4 and Interleukin-13 Signaling Connections Maps
Science, June 6, 2003; 300(5625): 1527 - 1528.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
C. Vasu, S. R. Gorla, B. S. Prabhakar, and M. J. Holterman
Targeted engagement of CTLA-4 prevents autoimmune thyroiditis
Int. Immunol., May 1, 2003; 15(5): 641 - 654.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. A. Bruns, U. Schindler, and M. H. Kaplan
Expression of a Constitutively Active Stat6 In Vivo Alters Lymphocyte Homeostasis with Distinct Effects in T and B Cells
J. Immunol., April 1, 2003; 170(7): 3478 - 3487.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
E. V. Acosta Rodriguez, E. Zuniga, C. L. Montes, and A. Gruppi
Interleukin-4 biases differentiation of B cells from Trypanosoma cruzi-infected mice and restrains their fratricide: role of Fas ligand down-regulation and MHC class II-transactivator up-regulation
J. Leukoc. Biol., January 1, 2003; 73(1): 127 - 136.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement