Gene Expression of TLR2 in Lung and Its Potential Signal Transduction Mechanism in a Mouse Model of Chlamydia Pneumoniae Pneumonitis_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

DONG Jing ¹ ,  SHI Yi ² , SONG Yong ² , SONG Yingjian. ²

Emergency Center of Nanjing Chest Hospital. Nanjing, Jiangsu, 210029, China;

Corresponding author：

SHI Yi, Email: shiyi56@126.com

Keywords：

Chlamydia Pneumoniae; Pneumonitis; Toll-like receptor; Signal pathway; SB203580; Pyrrolidine dithiocarbamate; p38MAPK; Nuclear factor kappa B

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Objective To investigate changes of TLR2 mRNA expression in lung of a mouse model of Chlamydia Pneumoniae pneumonitis, and to explore the possible mechanism of signal transduction. Methods Ninety-six male C3H/HeJ mice were randomly divided into four groups as follows: a control group, a model group, a SB203580 intervened group, and a pyrrolidine dithiocarbamate( PDTC) intervened group. Chlamydia Pneumoniae pneumonitis was induced by intranasally inoculated with 4. 0 ×106 IFU/mL of C. Pneumoniae per mouse in the model group and two intervened groups. Then the intervened groups were intraperitoneally injected with the p38MAPK inhibitor SB203580 and nuclear factor kappa B ( NF-κB)inhibitor PDTC, respectively. Six mice in each group were randomly killed in 1st, 4th, 7th and 14th day. The expressional changes of TLR2 mRNA in the mice lung tissue were measured by semi-quantitative RT-PCR. The concentrations of TNF-α in the lung homogenate were measured by ELISA. Results TLR2 mRNA expression in the lung tissue significantly increased after C. Pneumoniae infection, peaking at 4th and 7th days, then decreased after 14th day. Tumor necrosis factor-α( TNF-α) was also elevated in the lung tissue after C. Pneumoniae challenging. Both SB203580 and PDTC treatment effectively inhibited TNF-αand TLR2 mRNA expressions in lung. The inhibitory effect was more obvious by SB203580 treatment. Conclusion C. Pneumoniae can upregulate the expressions of TLR2 and TNF-α in lung, and TLR2/MAPK and TLR2 /NF-κB signal pathways may be involved in Chlamydia Pneumoniae pneumonitis.

Citation： DONG Jing,SHI Yi,SONG Yong,SONG Yingjian.. Gene Expression of TLR2 in Lung and Its Potential Signal Transduction Mechanism in a Mouse Model of Chlamydia Pneumoniae Pneumonitis. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(3): 267-270. doi: Copy

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8.	董静, 施毅, 宋勇, 等. 小鼠感染肺炎衣原体后肺组织TLR2、TLR4 基因表达变化及意义. 中国抗感染化疗杂志, 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. 董静, 施毅, 宋勇, 等. 小鼠感染肺炎衣原体后肺组织TLR2、TLR4 基因表达变化及意义. 中国抗感染化疗杂志, 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.

Chinese Journal of Respiratory and Critical Care Medicine

Gene Expression of TLR2 in Lung and Its Potential Signal Transduction Mechanism in a Mouse Model of Chlamydia Pneumoniae Pneumonitis

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