組蛋白修飾對COPD 大鼠肺泡Ⅱ 型上皮細胞趨化因子表達的影響_《中國呼吸與危重監護雜志》

作者：

甘麗杏 , 李成業 , 郭雪君

上海交通大學醫學院附屬新華醫院呼吸科( 上海 200092)通訊作者: 郭雪君, E-mail: guoxjz@ yahoo. com. cn;

關鍵詞：

慢性阻塞性肺疾病肺泡Ⅱ型上皮細胞組蛋白去乙酰化酶趨化因子

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目的探討COPD 大鼠肺泡Ⅱ型上皮細胞( AECⅡ) 炎癥因子表達是否與組蛋白修飾有關。方法熏煙法建立大鼠COPD 模型。取大鼠肺組織進行病理觀察, 提取AECⅡ 進行堿性磷酸酶染色鑒定和電鏡鑒定; 實時定量PCR 檢測AECⅡ 三種趨化因子: 單核細胞趨化蛋白1( MCP-1) 、IL-8及巨噬細胞炎性蛋白2α( MIP-2α) 的mRNA 表達; Western blot 檢測組蛋白去乙酰化酶2( HDAC2) 蛋白表達; 染色質免疫共沉淀( ChIP) 檢測趨化因子啟動子區組蛋白H3、H4 乙酰化和H4K9甲基化修飾情況。結果 COPD 組IL-8、MCP-1、MIP-2αmRNA 表達較正常對照組分別增加4. 48 倍、3. 14 倍、2. 83 倍; COPD組AECⅡ細胞HDAC2 蛋白表達較正常對照組降低( 0. 25 ±0. 15 比0. 66 ±0. 15,P lt;0. 05) , 且HDAC2 的下降程度與IL-8、MCP-1、MIP-2αmRNA 表達增高程度呈負相關( r 值分別為- 0. 960、- 0. 914、- 0. 928, P 均 lt;0. 05) 。COPD 組趨化因子基因啟動子區H3、H4 乙酰化水平較正常對照組均升高, H4K9 甲基化水平則降低( P 均 lt; 0. 05) 。結論 COPD 模型大鼠AECⅡ的IL-8、MCP-1、MIP-2α三種趨化因子基因表達增加, HDAC2 介導的組蛋白修飾在COPD炎癥反應中發揮重要作用。

引用本文： 甘麗杏,李成業,郭雪君. 組蛋白修飾對COPD 大鼠肺泡Ⅱ 型上皮細胞趨化因子表達的影響. 中國呼吸與危重監護雜志, 2010, 9(4): 360-364. doi: 復制

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8.	Ashburner BP, Westerheide SD, Baldwin AS Jr. The p65 ( RelA)subunit of NF- κB interacts with the histone deacetylase ( HDAC)corepressors HDAC1 and HDAC2 to negatively regulate gene expression.Mol Cell Biol, 2001 , 21: 7065-7077.
9.	Ito K, Adcock IM. Histone acetylation and histone deacetylation.Mol Biotechnol, 2002 , 20: 99-106 .
10.	Celli BR, Barnes PJ. Exacerbations of chronic obstructive pulmonary disease. Eur Respir J, 2007, 29: 1224-1238.
11.	Szulakowski P, Crowther AJL, Jimenez LA, et al. The effect of smoking on the transcriptional regulation of lung inflammation inpatients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2006, 174: 41-50.
12.	Rajendrasozhan S, Yang SR, Edirisinghe I, et al. Deacetylases and NF-kappaB in redox regulation of cigarette smoke-induced lung inflammation: epigenetics in pathogenesis of COPD. Antioxid Redox Signal, 2008, 10: 799-812 .
13.	Barnes PJ. Role of HDAC2 in the pathophysiology of COPD. Annu Rev Physiol, 2009, 71 : 451-464.
14.	Ito K, Yamamura S, Essilfie-Quaye S, et al. Histone deacetylase 2 -mediated deacetylation of the glucocorticoid receptor enables NFkappaB suppression. J Exp Med, 2006, 203: 7-13.

1. Adcock IM, Tsaprouni L, Bhavsar P, et al. Epigenetic regulation of airway inflammation. Curr Opin Immunol, 2007 , 19: 694 -700.
2. 田素增, 謝敏, 劉濤, 等. 慢性阻塞性肺疾病大鼠Ⅱ 型肺泡上皮細胞凋亡水平的變化及吸入糖皮質激素對其的影響. 中國呼吸與危重監護雜志, 2007, 6 : 381-384.
3. Barnes PJ, Adcock IM. Glucocorticoid resistance in inflammatory disease. Lancet, 2009, 373: 1905-1917.
4. Dobbs LG, Williams MC. An improved method for isolating typeⅡcells in high yield and purity. Rev Rispir Dis, 1986, 134 : 141-145.
5. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real -time quantitative PCR and the 2 ( -Delta Delta C( T) ) .Methods, 2001 , 25: 402-408.
6. 張斌, 何威, 楊揚, 等. 體外培養人皮膚鱗狀細胞癌A431 細胞Smad2 和Smad3 mRNA 的表達. 臨床皮膚科雜志, 2008, 37: 290 -292.
7. Ito K, Barnes PJ, Adcock IM. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1beta-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol, 2000, 20: 6891 -6903.
8. Ashburner BP, Westerheide SD, Baldwin AS Jr. The p65 ( RelA)subunit of NF- κB interacts with the histone deacetylase ( HDAC)corepressors HDAC1 and HDAC2 to negatively regulate gene expression.Mol Cell Biol, 2001 , 21: 7065-7077.
9. Ito K, Adcock IM. Histone acetylation and histone deacetylation.Mol Biotechnol, 2002 , 20: 99-106 .
10. Celli BR, Barnes PJ. Exacerbations of chronic obstructive pulmonary disease. Eur Respir J, 2007, 29: 1224-1238.
11. Szulakowski P, Crowther AJL, Jimenez LA, et al. The effect of smoking on the transcriptional regulation of lung inflammation inpatients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2006, 174: 41-50.
12. Rajendrasozhan S, Yang SR, Edirisinghe I, et al. Deacetylases and NF-kappaB in redox regulation of cigarette smoke-induced lung inflammation: epigenetics in pathogenesis of COPD. Antioxid Redox Signal, 2008, 10: 799-812 .
13. Barnes PJ. Role of HDAC2 in the pathophysiology of COPD. Annu Rev Physiol, 2009, 71 : 451-464.
14. Ito K, Yamamura S, Essilfie-Quaye S, et al. Histone deacetylase 2 -mediated deacetylation of the glucocorticoid receptor enables NFkappaB suppression. J Exp Med, 2006, 203: 7-13.

《中國呼吸與危重監護雜志》

組蛋白修飾對COPD 大鼠肺泡Ⅱ 型上皮細胞趨化因子表達的影響

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《中國呼吸與危重監護雜志》

組蛋白修飾對COPD 大鼠肺泡Ⅱ 型上皮細胞趨化因子表達的影響

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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Content

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