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Blood, 15 July 2006, Vol. 108, No. 2, pp. 518-524. Prepublished online as a Blood First Edition Paper on April 11, 2006; DOI 10.1182/blood-2005-09-3691. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-09-3691v1 108/2/518    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Deng, W.-G. Articles by Wu, K. K Search for Related Content PubMed PubMed Citation Articles by Deng, W.-G. Articles by Wu, K. K Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 14, 2005 Accepted February 24, 2006 Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding Wu-Guo Deng, Shao-Tzu Tang, Hui-Ping Tseng, and Kenneth K Wu* Vascular Biology Research Center, Institute of Molecular Medicine & Division of Hematology, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA * Corresponding author; email: kenneth.k.wu{at}uth.tmc.edu. Melatonin has been shown to be produced by non-pineal cells and possess anti-inflammatory actions in animal models. In the present study, we tested the hypothesis that melatonin suppresses the expression of pro-inflammatory genes such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) by a common transcriptional mechanism. Melatonin but not tryptophan or serotonin inhibited lipopolysaccharide (LPS)-induced COX-2 and iNOS protein levels and promoter activities in RAW 264.7 in a time- and concentration-dependent manner. LPS or LPS plus interferon- (IFN) increased binding of all five isoforms of NF-B to COX-2 and iNOS promoters. Melatonin selectively inhibited p52 binding without affecting p100 expression, p52 generation from p100 or p52 nuclear translocation. p52 acetylation was enhanced by LPS which was abrogated by melatonin. Melatonin inhibited p300 histone acetyltransferase (HAT) activity and abrogated p300-augmented COX-2 and iNOS expression. HAT inhibitors suppressed LPS-induced p52 binding and acetylation to an extent similar to melatonin and melatonin did not potentiate the effect of HAT inhibitors. These results suggest that melatonin inhibits COX-2 and iNOS transcriptional activation by inhibiting p300 HAT activity thereby suppressing p52 acetylation, binding and transactivation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Wan and M. J. Lenardo Specification of DNA Binding Activity of NF-{kappa}B Proteins Cold Spring Harb Perspect Biol, October 1, 2009; 1(4): a000067 - a000067. [Abstract] [Full Text] [PDF] W.-G. Deng, G. Jayachandran, G. Wu, K. Xu, J. A. Roth, and L. Ji Tumor-specific Activation of Human Telomerase Reverses Transcriptase Promoter Activity by Activating Enhancer-binding Protein-2beta in Human Lung Cancer Cells J. Biol. Chem., September 7, 2007; 282(36): 26460 - 26470. [Abstract] [Full Text] [PDF] C.-H. Tang, D.-Y. Lu, T.-W. Tan, W.-M. Fu, and R.-S. Yang Ultrasound Induces Hypoxia-inducible Factor-1 Activation and Inducible Nitric-oxide Synthase Expression through the Integrin/Integrin-linked Kinase/Akt/Mammalian Target of Rapamycin Pathway in Osteoblasts J. Biol. Chem., August 31, 2007; 282(35): 25406 - 25415. [Abstract] [Full Text] [PDF] W.-G. Deng, A. J. Montero, and K. K. Wu Interferon-{gamma} Suppresses Cyclooxygenase-2 Promoter Activity by Inhibiting C-Jun and C/EBP{beta} Binding Arterioscler Thromb Vasc Biol, August 1, 2007; 27(8): 1752 - 1759. [Abstract] [Full Text] [PDF]

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