HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 8, 6658-6665, February 20, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/8/6658    most recent M306267200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Joo, M. Articles by Christman, J. W. Search for Related Content PubMed PubMed Citation Articles by Joo, M. Articles by Christman, J. W. Social Bookmarking                      What's this?

Transcriptional Regulation of the Cyclooxygenase-2 Gene in Macrophages by PU.1^*

Myungsoo Joo, Gye Young Park, Jeffrey G. Wright, Timothy S. Blackwell, Michael L. Atchison¶, and John W. Christman||

From the Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2650, the Department of Veterans Affairs Medical Center, Nashville, Tennessee 37203, and the ^¶Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Macrophages are an abundant source of cyclooxygenase-2 (COX-2) enzymatic products, but a specific mechanism for macrophage COX-2 gene expression has not been described. We examined whether PU.1, a myeloid-specific Ets family transcription factor, is involved. Sequence analysis revealed two potential c-Ets binding sites in the COX-2 promoter (COX-2p) which bind to immunoreactive PU.1. Chromatin immunoprecipitation analysis shows inducible PU.1 binding to these sites in response to lipopolysaccharide, and COX-2 protein production is augmented by ectopic expression of PU.1 but not by PU.1^S148A, indicating that PU.1 phosphorylation is likely involved. Interestingly, expression of PU.1 results in acetylation of CCAAT/enhancer-binding protein- (C/EBP-) and increased production of COX-2 protein. Coimmunoprecipitation experiments suggest a role for p300 in C/EBP- acetylation and COX-2 expression. In contrast, E1A inhibits acetylation of C/EBP- and is correlated with decreased COX-2 expression. Together, these data suggest that PU.1 is activated by phosphorylation of Ser¹⁴⁸ in response to lipopolysaccharide treatment and subsequently binds to sequences in the endogenous COX-2p in a time-dependent manner. Concomitantly, C/EBP- becomes acetylated, and expression of the COX-2 gene increases. We speculate that a combinatorial role of PU.1 and C/EBP- mediates the robust production of COX-2 products by macrophages which occurs in Gram-negative bacterial sepsis.

Received for publication, June 13, 2003 , and in revised form, December 3, 2003.

^* This work was supported by the Department of Veterans Affairs and National Institutes of Health Grants HL 68121, HL 66196, HL 07123, and GM 42415. 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.

^|| To whom correspondence should be addressed: Dept. of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, 1161 21st Ave. South, Suite T-1217 MCN, Nashville, TN 37232-2650. Tel.: 615-327-4387 (ext. 7921); Fax: 615-340-2347; E-mail: john.christman{at}vanderbilt.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. N. Ballinger, L. L. N. Hubbard, T. R. McMillan, G. B. Toews, M. Peters-Golden, R. Paine III, and B. B. Moore Paradoxical role of alveolar macrophage-derived granulocyte-macrophage colony-stimulating factor in pulmonary host defense post-bone marrow transplantation Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L114 - L122. [Abstract] [Full Text] [PDF]

				A. C. Azim, X. Wang, G. Y. Park, R. T. Sadikot, H. Cao, B. Mathew, M. Atchison, R. B. van Breemen, M. Joo, and J. W. Christman NF-{kappa}B-Inducing Kinase Regulates Cyclooxygenase 2 Gene Expression in Macrophages by Phosphorylation of PU.1 J. Immunol., December 1, 2007; 179(11): 7868 - 7875. [Abstract] [Full Text] [PDF]

				B. Csoka, Z. H. Nemeth, L. Virag, P. Gergely, S. J. Leibovich, P. Pacher, C.-X. Sun, M. R. Blackburn, E. S. Vizi, E. A. Deitch, et al. A2A adenosine receptors and C/EBP{beta} are crucially required for IL-10 production by macrophages exposed to Escherichia coli Blood, October 1, 2007; 110(7): 2685 - 2695. [Abstract] [Full Text] [PDF]

				A. C. Azim, H. Cao, X. Gao, M. Joo, A. B. Malik, R. B. van Breemen, R. T. Sadikot, G. Park, and J. W. Christman Regulation of cyclooxygenase-2 expression by small GTPase Rac2 in bone marrow macrophages Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L668 - L673. [Abstract] [Full Text] [PDF]

				M. Joo, M. Kwon, R. T. Sadikot, P. J. Kingsley, L. J. Marnett, T. S. Blackwell, R. S. Peebles Jr, Y. Urade, and J. W. Christman Induction and Function of Lipocalin Prostaglandin D Synthase in Host Immunity J. Immunol., August 15, 2007; 179(4): 2565 - 2575. [Abstract] [Full Text] [PDF]

				M. Joo, J. G. Wright, N. N. Hu, R. T. Sadikot, G. Y. Park, T. S. Blackwell, and J. W. Christman Yin Yang 1 enhances cyclooxygenase-2 gene expression in macrophages Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1219 - L1226. [Abstract] [Full Text] [PDF]

				T. I. Cesena, J.-R. Cardinaux, R. Kwok, and J. Schwartz CCAAT/Enhancer-binding Protein (C/EBP) beta Is Acetylated at Multiple Lysines: ACETYLATION OF C/EBPbeta AT LYSINE 39 MODULATES ITS ABILITY TO ACTIVATE TRANSCRIPTION J. Biol. Chem., January 12, 2007; 282(2): 956 - 967. [Abstract] [Full Text] [PDF]

				Y.-J. Kang, B. A. Wingerd, T. Arakawa, and W. L. Smith Cyclooxygenase-2 Gene Transcription in a Macrophage Model of Inflammation J. Immunol., December 1, 2006; 177(11): 8111 - 8122. [Abstract] [Full Text] [PDF]

				G. Y. Suh, Y. Jin, A.-K. Yi, X. M. Wang, and A. M. K. Choi CCAAT/Enhancer-Binding Protein Mediates Carbon Monoxide-Induced Suppression of Cyclooxygenase-2 Am. J. Respir. Cell Mol. Biol., August 1, 2006; 35(2): 220 - 226. [Abstract] [Full Text] [PDF]

				H. T. Aung, K. Schroder, S. R. Himes, K. Brion, W. van Zuylen, A. Trieu, H. Suzuki, Y. Hayashizaki, D. A. Hume, M. J. Sweet, et al. LPS regulates proinflammatory gene expression in macrophages by altering histone deacetylase expression FASEB J, July 1, 2006; 20(9): 1315 - 1327. [Abstract] [Full Text] [PDF]

				G. Y. Park and J. W. Christman Involvement of cyclooxygenase-2 and prostaglandins in the molecular pathogenesis of inflammatory lung diseases Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L797 - L805. [Abstract] [Full Text] [PDF]

				J.-M. Wang, C.-Y. Ko, L.-C. Chen, W.-L. Wang, and W.-C. Chang Functional role of NF-IL6{beta} and its sumoylation and acetylation modifications in promoter activation of cyclooxygenase 2 gene Nucleic Acids Res., January 5, 2006; 34(1): 217 - 231. [Abstract] [Full Text] [PDF]

				Y. Wang, R. M. Baron, G. Zhu, M. Joo, J. W. Christman, E. S. Silverman, M. A. Perrella, R. J. Riese, and M. Cernadas PU.1 Regulates Cathepsin S Expression in Professional APCs J. Immunol., January 1, 2006; 176(1): 275 - 283. [Abstract] [Full Text] [PDF]

				T. V. Pedchenko, G. Y. Park, M. Joo, T. S. Blackwell, and J. W. Christman Inducible binding of PU.1 and interacting proteins to the Toll-like receptor 4 promoter during endotoxemia Am J Physiol Lung Cell Mol Physiol, September 1, 2005; 289(3): L429 - L437. [Abstract] [Full Text] [PDF]

				H. Zhong, A. Takeda, R. Nazari, H. Shio, G. Blobel, and N. R. Yaseen Carrier-independent Nuclear Import of the Transcription Factor PU.1 via RanGTP-stimulated Binding to Nup153 J. Biol. Chem., March 18, 2005; 280(11): 10675 - 10682. [Abstract] [Full Text] [PDF]