小鼠肺炎衣原體肺炎TLR2基因表達及信號傳導機制的實驗研究_《中國呼吸與危重監護雜志》

作者：

董靜 ¹ ,  施毅 ² , 宋勇 ² , 宋應健 ²

1 南京市胸科醫院（江蘇南京210029）;;
2南京軍區南京總醫院呼吸科（江蘇南京 210002）;

關鍵詞：

肺炎衣原體肺炎 TOLL樣受體信號傳導通路 SB203580 吡咯烷二硫氨基甲酸 p38蛋白激酶核因子κB

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目的探討小鼠感染肺炎衣原體后肺組織TOLL 樣受體( TLR) 2 的基因表達變化及其信號傳導機制。方法 TLR4 基因缺失小鼠( C3H/HeJ) 96 只, 隨機分為對照組、模型組、SB203580 組和PDTC 組, 每組24 只。每組分別按1、4、7、14 d 各分4 個小組, 每小組6 只。對照組鼻內接種二磷酸蔗糖( 2sp) 緩沖液, 模型組和干預組均給予約4. 0 ×106 IFU/mL( 0. 04 mL) 的肺炎衣原體鼻內接種,SB203580 組和PDTC 組在接種完肺炎衣原體后分別立即腹腔注射相應的p38 蛋白激酶( p38MAPK)抑制劑SB203580 ( 100 mg/ kg ) 或核因子κB ( NF-κB) 抑制劑吡咯烷二硫氨基甲酸( PDTC)( 50 mg/kg) 。分別于接種后第1、4、7 及14 d 處死小鼠, RT-PCR 法檢測肺組織TLR2 mRNA 的表達,ELISA 法測定肺組織勻漿腫瘤壞死因子α( TNF-α) 的含量, 同時觀察肺組織病理變化。結果小鼠感染肺炎衣原體后肺組織TLR2 mRNA 表達迅速升高, 以第4 d 和第7 d 明顯, 14 d 以后開始下降。PDTC 早期干預可在一定程度上抑制肺臟組織TLR2 mRNA 表達, 并在感染高峰期抑制明顯。SB203580 對小鼠肺組織TLR2 mRNA 表達也有明顯抑制。感染肺炎衣原體后, 肺組織TNF-α表達水平顯著高于正常組, SB203580 和PDTC 對小鼠肺組織TNF-α表達均有抑制作用, SB203580 對TNF-α的抑制作用強于PDTC。結果小鼠感染肺炎衣原體后, 可引起TLR2 表達的增加。對p38MAPK 和 NF-κB 的干預均影響TLR2 的表達以及炎癥介質的釋放, 提示肺炎衣原體可能是通過TLR2 /MAPK 和TLR2 /NF-κB 通路導致肺部炎癥反應。

引用本文： 董靜,施毅,宋勇,宋應健. 小鼠肺炎衣原體肺炎TLR2基因表達及信號傳導機制的實驗研究. 中國呼吸與危重監護雜志, 2009, 09(3): 267-270. doi: 復制

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5.	Sasu S, LaVerda D, Qureshi N, et al. Chlamydia pneumoniae and chlamydial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via toll-like receptor 4 and p44 /p42 mitogen-activated protein kinase activation. Circ Res, 2001, 89: 244-250.
6.	Netea MG, Kullberg BJ, Galama JM, et al. Non-LPS components of Chlamydia pneumonoae stimulate cytokinr production through Tolllike receptor 2-dependent pathways. Eur J Immunol, 2002, 32: 1188-1195.
7.	Bulut Y, Faure E, Thomas L, et al. Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway. Immunol,2002, 168: 1435-1440.
8.	董靜, 施毅, 宋勇, 等. 小鼠感染肺炎衣原體后肺組織TLR2、TLR4 基因表達變化及意義. 中國抗感染化療雜志, 2006, 6: 92-96.
9.	Cuzzocrea S, Chatterjee PK, Mazzon E, et al. Pyrrolidine dithiocarbamate attenuates the development of acute and chronic inflammation. Br J Pharmacol, 2002, 135: 496-510.
10.	Wissel H, Schulz C, Koehne P, et al. Chlamydophila pneumoniae induces expression of Toll-like Receptor 4 and release of TNF-αand MIP-2 via an NF-κB pathway in rat type II pneumocytes. Respir Res, 2005, 6: 51-56.

1. Armant MA, Fenton MJ. Toll-like receptors: a family of patternrecognition receptors in mammals. Genome Biol, 2002, 3: 3011-3016.
2. Perera PY, Mayadas TN, Takeuchi O, et al. CD11b /CD18 acts in concert with CD14 and Toll-like receptor ( TLR ) 4 to elicit full lipopolysaccharide and taxol-inducible gene expression. J Immunol,2001, 166: 574-581.
3. Costa CP, Kirschning CJ, Busch D, et al. Role of chlamydial heat shock protein 60 in the stimulation of innate immune cells by Chlamydia pneumoniae. Eur J Immunol, 2002, 32: 2460-2470.
4. Prebeck S, Kirschning C, Dürr S, et al. Predominant role of toll-like receptor 2 versus 4 in Chlamydia pneumonoae-induced activation of dendritic cells. J Immunol, 2001, 167: 3316-3323.
5. Sasu S, LaVerda D, Qureshi N, et al. Chlamydia pneumoniae and chlamydial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via toll-like receptor 4 and p44 /p42 mitogen-activated protein kinase activation. Circ Res, 2001, 89: 244-250.
6. Netea MG, Kullberg BJ, Galama JM, et al. Non-LPS components of Chlamydia pneumonoae stimulate cytokinr production through Tolllike receptor 2-dependent pathways. Eur J Immunol, 2002, 32: 1188-1195.
7. Bulut Y, Faure E, Thomas L, et al. Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway. Immunol,2002, 168: 1435-1440.
8. 董靜, 施毅, 宋勇, 等. 小鼠感染肺炎衣原體后肺組織TLR2、TLR4 基因表達變化及意義. 中國抗感染化療雜志, 2006, 6: 92-96.
9. Cuzzocrea S, Chatterjee PK, Mazzon E, et al. Pyrrolidine dithiocarbamate attenuates the development of acute and chronic inflammation. Br J Pharmacol, 2002, 135: 496-510.
10. Wissel H, Schulz C, Koehne P, et al. Chlamydophila pneumoniae induces expression of Toll-like Receptor 4 and release of TNF-αand MIP-2 via an NF-κB pathway in rat type II pneumocytes. Respir Res, 2005, 6: 51-56.

《中國呼吸與危重監護雜志》

小鼠肺炎衣原體肺炎TLR2基因表達及信號傳導機制的實驗研究

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《中國呼吸與危重監護雜志》

小鼠肺炎衣原體肺炎TLR2基因表達及信號傳導機制的實驗研究

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