目的 探討COPD 大鼠肺泡Ⅱ型上皮細(xì)胞( AECⅡ) 炎癥因子表達(dá)是否與組蛋白修飾有關(guān)。方法 熏煙法建立大鼠COPD 模型。取大鼠肺組織進(jìn)行病理觀察, 提取AECⅡ 進(jìn)行堿性磷酸酶染色鑒定和電鏡鑒定; 實(shí)時(shí)定量PCR 檢測(cè)AECⅡ 三種趨化因子: 單核細(xì)胞趨化蛋白1( MCP-1) 、IL-8及巨噬細(xì)胞炎性蛋白2α( MIP-2α) 的mRNA 表達(dá); Western blot 檢測(cè)組蛋白去乙?；?( HDAC2) 蛋白表達(dá); 染色質(zhì)免疫共沉淀( ChIP) 檢測(cè)趨化因子啟動(dòng)子區(qū)組蛋白H3、H4 乙?；虷4K9甲基化修飾情況。結(jié)果 COPD 組IL-8、MCP-1、MIP-2αmRNA 表達(dá)較正常對(duì)照組分別增加4. 48 倍、3. 14 倍、2. 83 倍; COPD組AECⅡ細(xì)胞HDAC2 蛋白表達(dá)較正常對(duì)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(dá)增高程度呈負(fù)相關(guān)( 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(dòng)子區(qū)H3、H4 乙?；捷^正常對(duì)照組均升高, H4K9 甲基化水平則降低( P 均 lt; 0. 05) 。結(jié)論 COPD 模型大鼠AECⅡ的IL-8、MCP-1、MIP-2α三種趨化因子基因表達(dá)增加, HDAC2 介導(dǎo)的組蛋白修飾在COPD炎癥反應(yīng)中發(fā)揮重要作用。
引用本文： 甘麗杏,李成業(yè),郭雪君. 組蛋白修飾對(duì)COPD 大鼠肺泡Ⅱ 型上皮細(xì)胞趨化因子表達(dá)的影響. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2010, 9(4): 360-364. doi: 復(fù)制
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| 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(xì)胞凋亡水平的變化及吸入糖皮質(zhì)激素對(duì)其的影響. 中國(guó)呼吸與危重監(jiān)護(hù)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(yáng), 等. 體外培養(yǎng)人皮膚鱗狀細(xì)胞癌A431 細(xì)胞Smad2 和Smad3 mRNA 的表達(dá). 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. |
- 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(xì)胞凋亡水平的變化及吸入糖皮質(zhì)激素對(duì)其的影響. 中國(guó)呼吸與危重監(jiān)護(hù)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(yáng), 等. 體外培養(yǎng)人皮膚鱗狀細(xì)胞癌A431 細(xì)胞Smad2 和Smad3 mRNA 的表達(dá). 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.