Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding.

Content Provider	Semantic Scholar
Author	Deng, Wu-Guo Tang, Shao-Tzu Tseng, Hui-Ping Wu, Kenneth K.
Copyright Year	2006
Abstract	Melatonin has been shown to be produced by nonpineal cells and possess anti-inflammatory actions in animal models. In the present study, we tested the hypothesis that melatonin suppresses the expression of proinflammatory genes such as cyclooxygenase-2 (COX2) 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 cells in a time- and concentration-dependent manner. LPS or LPS plus interferon-gamma (IFNgamma) increased binding of all 5 isoforms of NF-kappaB 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.
Starting Page	391
Ending Page	396
Page Count	6
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.bloodjournal.org/content/bloodjournal/108/2/518.full.pdf?sso-checked=true
Alternate Webpage(s)	http://bloodjournal.hematologylibrary.org/content/108/2/518.full.pdf
Alternate Webpage(s)	http://www.bloodjournal.org/content/bloodjournal/early/2006/04/11/blood-2005-09-3691.full.pdf?sso-checked=true
PubMed reference number	16609073v1
Volume Number	108
Issue Number	2
Journal	Blood
Language	English
Access Restriction	Open
Subject Keyword	Acetylation Acyltransferase Animal Model E1A-Associated p300 Protein Histones Inhibition Interferon Type II Lipopolysaccharides Melatonin NF-kappa B NOS2A protein, human Nitric Oxide Synthase Type II Nuclear Translocation Protein Isoforms Serotonin Trans-Activation, Genetic Transcription, Genetic Transcriptional Activation Tryptophan cyclooxygenase 2 histone acetyltransferase promoter
Content Type	Text
Resource Type	Article