Advertisement
JBC

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


     

Originally published In Press as doi:10.1074/jbc.M308448200 on September 24, 2003

J. Biol. Chem., Vol. 278, Issue 49, 49378-49385, December 5, 2003
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
278/49/49378    most recent
M308448200v1
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 Dong, X.
Right arrow Articles by Griffin, M. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dong, X.
Right arrow Articles by Griffin, M. D.
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?

Direct Transcriptional Regulation of RelB by 1{alpha},25-Dihydroxyvitamin D3 and Its Analogs

PHYSIOLOGIC AND THERAPEUTIC IMPLICATIONS FOR DENDRITIC CELL FUNCTION*

Xiangyang Dong{ddagger}§, Theodore Craig{ddagger}, Nianzeng Xing{ddagger}, Lori A. Bachman{ddagger}, Carlos V. Paya||**, Falk Weih{ddagger}{ddagger}, David J. McKean**, Rajiv Kumar{ddagger}, and Matthew D. Griffin{ddagger}§§

From the {ddagger}Department of Internal Medicine, Division of Nephrology, the Department of Biochemistry and Molecular Biology and the Mayo Proteomics Research Center, the ||Department of Internal Medicine, Division of Infectious Diseases, and the **Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905 and the {ddagger}{ddagger}Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, Karlsruhe 76021, Germany

The nuclear factor-{kappa}B (NF-{kappa}B) protein RelB plays a unique role in dendritic cell (DC) function and, as such, is an important regulator of antigen presentation and immune regulation. In this study, inhibition of RelB expression in DCs exposed to an analog of the active form of vitamin D3 (1{alpha},25-dihydroxyvitamin D3 (1{alpha},25-(OH)2D3)) was observed and shown to be mediated by the vitamin D receptor (VDR). Potential vitamin D response elements were identified within promoter regions of human and mouse relB genes. In gel shift experiments, these motifs specifically bound VDR·retinoid X receptor-{alpha} complexes. Reporter assays confirmed that transcriptional activity of human and mouse relB promoters was inhibited by 1{alpha},25-(OH)2D3 agonists in a DC-derived cell line. The inhibition was abolished by mutagenesis of the putative vitamin D response elements and was enhanced by overexpression of VDR. Mutagenesis of NF-{kappa}B response elements within the relB promoter did not affect the magnitude of 1{alpha},25-(OH)2D3 analog-mediated inhibition, ruling out an indirect effect on NF-{kappa}B signaling. Glucocorticoid caused additional inhibition of relB promoter activity when combined with the 1{alpha},25-(OH)2D3 analog. This effect was dependent on the integrity of the NF-{kappa}B response elements, suggesting separate regulatory mechanisms for the two steroid pathways on this promoter. We conclude that relB is a direct target for 1{alpha},25-(OH)2D3-mediated negative transcriptional regulation via binding of VDR·retinoid X receptor-{alpha} to discrete DNA motifs. This mechanism has important implications for the inhibitory effect of 1{alpha},25-(OH)2D3 on DC maturation and for the potential immunotherapeutic use of 1{alpha},25-(OH)2D3 analogs alone or combined with other agents.

Received for publication, August 1, 2003 , and in revised form, September 22, 2003.

* This work was supported in part by National Institutes of Health Grant DK59505 (to M. D. G.) and Grants DK25409 and DK58546 (to R. K.) and by the Mayo Foundation CR75 Program (to M. D. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Supported by National Institutes of Health Training Grant T32DK07013 (to the Mayo Foundation Division of Nephrology).

§§ To whom correspondence should be addressed: Dept. of Internal Medicine, Div. of Nephrology, Mayo Clinic and Foundation, Charlton 10 Transplant Center, 200 First St. SW, Rochester, MN 55905. Tel.: 507-266-6953; Fax: 507-266-1069; E-mail: griffin.matthew{at}mayo.edu.


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
 Am. J. Physiol. Renal Physiol.Home page
D. K. Deb, Y. Chen, Z. Zhang, Y. Zhang, F. L. Szeto, K. E. Wong, J. Kong, and Y. C. Li
1,25-Dihydroxyvitamin D3 suppresses high glucose-induced angiotensinogen expression in kidney cells by blocking the NF-{kappa}B pathway
Am J Physiol Renal Physiol, May 1, 2009; 296(5): F1212 - F1218.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. A. Taher, B. C. A. M. van Esch, G. A. Hofman, P. A. J. Henricks, and A. J. M. van Oosterhout
1{alpha},25-Dihydroxyvitamin D3 Potentiates the Beneficial Effects of Allergen Immunotherapy in a Mouse Model of Allergic Asthma: Role for IL-10 and TGF-{beta}
J. Immunol., April 15, 2008; 180(8): 5211 - 5221.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
Y. Xu, F. Fang, D. K. St. Clair, S. Josson, P. Sompol, I. Spasojevic, and W. H. St. Clair
Suppression of RelB-mediated manganese superoxide dismutase expression reveals a primary mechanism for radiosensitization effect of 1{alpha},25-dihydroxyvitamin D3 in prostate cancer cells
Mol. Cancer Ther., July 1, 2007; 6(7): 2048 - 2056.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
G. Penna, S. Amuchastegui, N. Giarratana, K. C. Daniel, M. Vulcano, S. Sozzani, and L. Adorini
1,25-Dihydroxyvitamin D3 Selectively Modulates Tolerogenic Properties in Myeloid but Not Plasmacytoid Dendritic Cells
J. Immunol., January 1, 2007; 178(1): 145 - 153.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. Daniel, H. H. Radeke, N. A. Sartory, N. Zahn, U. Zuegel, A. Steinmeyer, and J. Stein
The New Low Calcemic Vitamin D Analog 22-Ene-25-Oxa-Vitamin D Prominently Ameliorates T Helper Cell Type 1-Mediated Colitis in Mice
J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 622 - 631.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. K. Yoza, J. Y.-Q. Hu, S. L. Cousart, L. M. Forrest, and C. E. McCall
Induction of RelB Participates in Endotoxin Tolerance
J. Immunol., September 15, 2006; 177(6): 4080 - 4085.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. Sun, J. Kong, Y. Duan, F. L. Szeto, A. Liao, J. L. Madara, and Y. C. Li
Increased NF-{kappa}B activity in fibroblasts lacking the vitamin D receptor
Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E315 - E322.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
E. G. Demicco, K. T. Kavanagh, R. Romieu-Mourez, X. Wang, S. R. Shin, E. Landesman-Bollag, D. C. Seldin, and G. E. Sonenshein
RelB/p52 NF-{kappa}B Complexes Rescue an Early Delay in Mammary Gland Development in Transgenic Mice with Targeted Superrepressor I{kappa}B-{alpha} Expression and Promote Carcinogenesis of the Mammary Gland
Mol. Cell. Biol., November 15, 2005; 25(22): 10136 - 10147.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
G. Penna, A. Roncari, S. Amuchastegui, K. C. Daniel, E. Berti, M. Colonna, and L. Adorini
Expression of the inhibitory receptor ILT3 on dendritic cells is dispensable for induction of CD4+Foxp3+ regulatory T cells by 1,25-dihydroxyvitamin D3
Blood, November 15, 2005; 106(10): 3490 - 3497.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
A. J. M. van Oosterhout and N. Bloksma
Regulatory T-lymphocytes in asthma
Eur. Respir. J., November 1, 2005; 26(5): 918 - 932.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
T.-T. Wang, L. E. Tavera-Mendoza, D. Laperriere, E. Libby, N. Burton MacLeod, Y. Nagai, V. Bourdeau, A. Konstorum, B. Lallemant, R. Zhang, et al.
Large-Scale in Silico and Microarray-Based Identification of Direct 1,25-Dihydroxyvitamin D3 Target Genes
Mol. Endocrinol., November 1, 2005; 19(11): 2685 - 2695.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
X. Dong, W. Lutz, T. M. Schroeder, L. A. Bachman, J. J. Westendorf, R. Kumar, and M. D. Griffin
Regulation of relB in dendritic cells by means of modulated association of vitamin D receptor and histone deacetylase 3 with the promoter
PNAS, November 1, 2005; 102(44): 16007 - 16012.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
P. J. Cejas, L. M. Carlson, D. Kolonias, J. Zhang, I. Lindner, D. D. Billadeau, L. H. Boise, and K. P. Lee
Regulation of RelB Expression during the Initiation of Dendritic Cell Differentiation
Mol. Cell. Biol., September 1, 2005; 25(17): 7900 - 7916.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
H. Du, G. S. Daftary, S. I. Lalwani, and H. S. Taylor
Direct Regulation of HOXA10 by 1,25-(OH)2D3 in Human Myelomonocytic Cells and Human Endometrial Stromal Cells
Mol. Endocrinol., September 1, 2005; 19(9): 2222 - 2233.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
S. Nagpal, S. Na, and R. Rathnachalam
Noncalcemic Actions of Vitamin D Receptor Ligands
Endocr. Rev., August 1, 2005; 26(5): 662 - 687.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. H. Tan, P. Sagoo, C. Chan, J. B. Yates, J. Campbell, S. C. Beutelspacher, B. M. J. Foxwell, G. Lombardi, and A. J. T. George
Inhibition of NF-{kappa}B and Oxidative Pathways in Human Dendritic Cells by Antioxidative Vitamins Generates Regulatory T Cells
J. Immunol., June 15, 2005; 174(12): 7633 - 7644.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
M. C. Gauzzi, C. Purificato, L. Conti, L. Adorini, F. Belardelli, and S. Gessani
IRF-4 expression in the human myeloid lineage: up-regulation during dendritic cell differentiation and inhibition by 1{alpha},25-dihydroxyvitamin D3
J. Leukoc. Biol., June 1, 2005; 77(6): 944 - 947.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. A. Lyakh, M. Sanford, S. Chekol, H. A. Young, and A. B. Roberts
TGF-{beta} and Vitamin D3 Utilize Distinct Pathways to Suppress IL-12 Production and Modulate Rapid Differentiation of Human Monocytes into CD83+ Dendritic Cells
J. Immunol., February 15, 2005; 174(4): 2061 - 2070.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Giarratana, G. Penna, S. Amuchastegui, R. Mariani, K. C. Daniel, and L. Adorini
A Vitamin D Analog Down-Regulates Proinflammatory Chemokine Production by Pancreatic Islets Inhibiting T Cell Recruitment and Type 1 Diabetes Development
J. Immunol., August 15, 2004; 173(4): 2280 - 2287.
[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 © 2003 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement