title: Suppression of lipopolysaccharide- and tumour necrosis factor-alpha-induced interleukin (IL)-8 expression by glucocorticoids involves changes in IL-8 promoter acetylation.
abstract: There is accumulating evidence that the transrepressional effect of glucocorticoids in down-regulating proinflammatory gene expression might be regulated by an action on histone acetylation. To investigate this, we studied the effect of two glucocorticoids (dexamethasone and triamcinolone acetonide) on reducing lipopolysaccharide (LPS)- and tumour necrosis factor (TNF)-alpha-induced interleukin (IL)-8 release in a monocytic cell line and two lymphocytic cell lines (HUT-78 and Jurkat). The effect of the histone deacetylase inhibitor trichostatin A (TSA) on LPS- and TNF-alpha-induced IL-8 release and its repression by glucocorticoids was also examined. LPS and TNF-alpha induced IL-8 release in all three cell lines and this induction was inhibited by both dexamethasone and triamcinolone. Pretreatment of cells with TSA enhanced basal and LPS- and TNFalpha-stimulated IL-8 release in all three cell lines. TSA also attenuated the inhibitory effect of glucocorticoids on stimulated IL-8 release. Chromatin immunoprecipitation assays confirmed that LPS and TNF-alpha enhanced histone acetylation at the IL-8 promoter and that this was inhibited by triamcinolone in all three cell types. Changes in histone acetylation at the IL-8 are important in its regulation by proinflammatory and anti-inflammatory agents, and modulation of this activity may have therapeutic potential in inflammatory conditions.
authors: Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors: L G
authors: LG
authors: Tsaprouni
authors: K
authors: K
authors: Ito
authors: I M
authors: IM
authors: Adcock
authors: N
authors: N
authors: Punchard
mesh_terms: D000107:Acetylation; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D011401:Promoter Regions, Genetic; D014222:Triamcinolone Acetonide / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D005938:Glucocorticoids; D006657:Histones; D006877:Hydroxamic Acids; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C012589:trichostatin A; D003907:Dexamethasone; D014222:Triamcinolone Acetonide
references: Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):3919-24
references: 10760263
references: ACS Chem Biol. 2006 Mar 17;1(2):69-72
references: 17163645
references: Genes Dev. 2000 Sep 15;14(18):2314-29
references: 10995388
references: Cell Mol Life Sci. 2001 May;58(5-6):728-36
references: 11437234
references: Mol Cell Biol. 2001 Oct;21(20):7065-77
references: 11564889
references: Curr Opin Oncol. 2001 Nov;13(6):477-83
references: 11673688
references: Mol Cell. 2002 Mar;9(3):625-36
references: 11931769
references: Br J Pharmacol. 2002 May;136(2):280-6
references: 12010777
references: Mol Cell Biochem. 2002 May-Jun;234-235(1-2):239-48
references: 12162440
references: Biochem Soc Trans. 2003 Feb;31(Pt 1):60-5
references: 12546654
references: Biochem Biophys Res Commun. 2003 Feb 7;301(2):572-7
references: 12565901
references: Am J Physiol Lung Cell Mol Physiol. 2003 Mar;284(3):L533-40
references: 12573991
references: Biochem J. 2003 Mar 15;370(Pt 3):737-49
references: 12429021
references: Biochem Biophys Res Commun. 2004 Feb 27;315(1):240-5
references: 15013452
references: Nature. 2004 May 27;429(6990):457-63
references: 15164071
references: Biochem Pharmacol. 2004 Sep 15;68(6):1255-67
references: 15313424
references: Mol Pharmacol. 1995 Oct;48(4):747-57
references: 7476903
references: Nucleic Acids Res. 1999 Feb 1;27(3):711-20
references: 9889264
references: Proc Am Thorac Soc. 2004;1(3):239-46
references: 16113441
references: Expert Opin Ther Targets. 2005 Dec;9(6):1111-21
references: 16300464
references: Crit Care Med. 2005 Dec;33(12 Suppl):S466-7
references: 16340423
references: J Allergy Clin Immunol. 2006 Mar;117(3):522-43
references: 16522450
references: Curr Drug Targets. 2006 Jun;7(6):675-81
references: 16787167
references: Brief Funct Genomic Proteomic. 2006 Sep;5(3):190-208
references: 16980317
references: Crit Rev Immunol. 2006;26(4):307-16
references: 17073556
references: J Immunol. 2006 Nov 15;177(10):7173-83
references: 17082635
references: COPD. 2005 Dec;2(4):445-55
references: 17147010
references: Mol Cell Biol. 2000 Sep;20(18):6891-903
references: 10958685