Suppression of lipopolysaccharide- and tumour necrosis factor-α-induced interleukin (IL)-8 expression by glucocorticoids involves changes in IL-8 promoter acetylation

被引:24
|
作者
Tsaprouni, L. G.
Ito, K.
Adcock, I. M.
Punchard, N.
机构
[1] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Airways Dis Sect, London SW3 6LY, England
[2] Univ Luton, Dept Hlth & Biol Sci, Luton LU1 3JU, Beds, England
来源
CLINICAL AND EXPERIMENTAL IMMUNOLOGY | 2007年 / 150卷 / 01期
基金
英国医学研究理事会;
关键词
histone acetylation; monocytes; T cells; triamcinolone; trichostatin A;
D O I
10.1111/j.1365-2249.2007.03484.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 TNF alpha-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.
引用
收藏
页码:151 / 157
页数:7
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