JBC PeproTech; Our Business is Cytokines!

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


     

Originally published In Press as doi:10.1074/jbc.M207470200 on January 14, 2003

J. Biol. Chem., Vol. 278, Issue 13, 10983-10992, March 28, 2003
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
278/13/10983    most recent
M207470200v1
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 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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wu, D.
Right arrow Articles by Meydani, S. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wu, D.
Right arrow Articles by Meydani, S. N.
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?

Ceramide-induced and Age-associated Increase in Macrophage COX-2 Expression Is Mediated through Up-regulation of NF-kappa B Activity*

Dayong WuDagger , Melissa MarkoDagger , Kate ClaycombeDagger §, K. Eric Paulson, and Simin Nikbin MeydaniDagger ||**

From the Dagger  Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, the  Department of Biochemistry, and the || Department of Pathology, Sackler Graduate School of Biomedical Sciences, Tufts University, Boston, Massachusetts 02111

We have shown that the age-associated increase in lipopolysaccharide (LPS)-stimulated macrophages (Mphi ) prostaglandin E2 (PGE2) production is because of ceramide-induced up-regulation of cyclooxygenase (COX)-2 transcription that leads to increased COX-2 expression and enzyme activity. To determine the mechanism of the age-related and ceramide-dependent increase in COX-2 transcription, we investigated the role of various transcription factors involved in COX-2 gene expression. The results showed that LPS-initiated activations of both consensus and COX-2-specific NF-kappa B, but not AP-1 and CREB, were significantly higher in Mphi from old mice than those from young mice. We further showed that the higher NF-kappa B activation in old Mphi was because of greater Ikappa B degradation in the cytoplasm and p65 translocation to the nucleus. An Ikappa B phosphorylation inhibitor, Bay 11-7082, inhibited NF-kappa B activation, as well as PGE2 production, COX activity, COX-2 protein, and mRNA expression in both young and old Mphi . Similar results were obtained by blocking NF-kappa B binding activity using a NF-kappa B decoy. Furthermore, NF-kappa B inhibition resulted in significantly greater reduction in PGE2 production and COX activity in old compared with young Mphi . Addition of ceramide to the young Mphi , in the presence or absence of LPS, increased NF-kappa B activation in parallel with PGE2 production. Bay 11-7082 or NF-kappa B decoy prevented this ceramide-induced increase in NF-kappa B binding activity and PGE2 production. These findings strongly suggest that the age-associated and ceramide-induced increase in COX-2 transcription is mediated through higher NF-kappa B activation, which is, in turn, because of a greater Ikappa B degradation in old Mphi .

* This work was supported by NIA National Institutes of Health Grant RO1-AG09140-09, National Institutes of Health Grant ES11518, and United States Department of Agriculture agreement 58-1950-9-001.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.

§ Current address: Food Science and Human Nutrition Department, Michigan State University, East Lansing, MI 48824.

** To whom correspondence should be addressed: Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111. Tel.: 617-556-3129; Fax: 617-556-3224; E-mail: smeydani@hnrc.tufts.edu.

Copyright © 2003 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
 FASEB J.Home page
Y.-Y. Liu, J. Y. Yu, D. Yin, G. A. Patwardhan, V. Gupta, Y. Hirabayashi, W. M. Holleran, A. E. Giuliano, S. M. Jazwinski, V. Gouaze-Andersson, et al.
A role for ceramide in driving cancer cell resistance to doxorubicin
FASEB J, July 1, 2008; 22(7): 2541 - 2551.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
K. Rutkute, R. H. Asmis, and M. N. Nikolova-Karakashian
Regulation of neutral sphingomyelinase-2 by GSH: a new insight to the role of oxidative stress in aging-associated inflammation
J. Lipid Res., November 1, 2007; 48(11): 2443 - 2452.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. Wu, Z. Ren, M. Pae, W. Guo, X. Cui, A. H. Merrill, and S. N. Meydani
Aging Up-Regulates Expression of Inflammatory Mediators in Mouse Adipose Tissue
J. Immunol., October 1, 2007; 179(7): 4829 - 4839.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
L. W. Maines, K. J. French, E. B. Wolpert, D. A. Antonetti, and C. D. Smith
Pharmacologic Manipulation of Sphingosine Kinase in Retinal Endothelial Cells: Implications for Angiogenic Ocular Diseases
Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 5022 - 5031.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. K. Kundu, Y. K. Shin, S. H. Kim, and Y.-J. Surh
Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-{kappa}B in mouse skin by blocking I{kappa}B kinase activity
Carcinogenesis, July 1, 2006; 27(7): 1465 - 1474.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. M. Blanco, S. L. Valles, M. Pascual, and C. Guerri
Involvement of TLR4/Type I IL-1 Receptor Signaling in the Induction of Inflammatory Mediators and Cell Death Induced by Ethanol in Cultured Astrocytes
J. Immunol., November 15, 2005; 175(10): 6893 - 6899.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
K. Nakamichi, M. Saiki, M. Sawada, M. Takayama-Ito, Y. Yamamuro, K. Morimoto, and I. Kurane
Rabies Virus-Induced Activation of Mitogen-Activated Protein Kinase and NF-{kappa}B Signaling Pathways Regulates Expression of CXC and CC Chemokine Ligands in Microglia
J. Virol., September 15, 2005; 79(18): 11801 - 11812.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
K. M. Ajuwon and M. E. Spurlock
Palmitate Activates the NF-{kappa}B Transcription Factor and Induces IL-6 and TNF{alpha} Expression in 3T3-L1 Adipocytes
J. Nutr., August 1, 2005; 135(8): 1841 - 1846.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Kim, S. H. Rhee, E. Kokkotou, X. Na, T. Savidge, M. P. Moyer, C. Pothoulakis, and J. T. LaMont
Clostridium difficile Toxin A Regulates Inducible Cyclooxygenase-2 and Prostaglandin E2 Synthesis in Colonocytes via Reactive Oxygen Species and Activation of p38 MAPK
J. Biol. Chem., June 3, 2005; 280(22): 21237 - 21245.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J.-H. Hung, I.-J. Su, H.-Y. Lei, H.-C. Wang, W.-C. Lin, W.-T. Chang, W. Huang, W.-C. Chang, Y.-S. Chang, C.-C. Chen, et al.
Endoplasmic Reticulum Stress Stimulates the Expression of Cyclooxygenase-2 through Activation of NF-{kappa}B and pp38 Mitogen-activated Protein Kinase
J. Biol. Chem., November 5, 2004; 279(45): 46384 - 46392.
[Abstract] [Full Text] [PDF]

Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
J. W. Kim, Y. Zou, S. Yoon, J. H. Lee, Y. K. Kim, B. P. Yu, and H. Y. Chung
Vascular Aging: Molecular Modulation of the Prostanoid Cascade by Calorie Restriction
J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2004; 59(9): B876 - B885.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
E. D. Boehmer, J. Goral, D. E. Faunce, and E. J. Kovacs
Age-dependent decrease in Toll-like receptor 4-mediated proinflammatory cytokine production and mitogen-activated protein kinase expression
J. Leukoc. Biol., February 1, 2004; 75(2): 342 - 349.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Pierer, J. Rethage, R. Seibl, R. Lauener, F. Brentano, U. Wagner, H. Hantzschel, B. A. Michel, R. E. Gay, S. Gay, et al.
Chemokine Secretion of Rheumatoid Arthritis Synovial Fibroblasts Stimulated by Toll-Like Receptor 2 Ligands
J. Immunol., January 15, 2004; 172(2): 1256 - 1265.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
F. Bea, E. Blessing, B. J Bennett, C. C. Kuo, L. A. Campbell, J. Kreuzer, and M. E Rosenfeld
Chronic inhibition of cyclooxygenase-2 does not alter plaque composition in a mouse model of advanced unstable atherosclerosis
Cardiovasc Res, October 15, 2003; 60(1): 198 - 204.
[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.