Methylprednisolone Alleviates Airway Inflammation of Chronic Bronchitis by Inhibiting the Expression of Phosphodiesterase 4D in Rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 LI li , WANG Xiangdong.

The Hospital of Science City.Mianyang, Sichuan, 621900, ChinaCorresponding Author: Li li, E-mail: llzp1035@ 163. com;

Corresponding author：

LI li, Email: llzp1035@163.com

Keywords：

Chronic bronchitis; Phosphodiesterase 4D; Methylprednisolone; Tumor necrosis factor-α

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Objective To investigate the effects of methylprednisolone on airway inflammation of chronic bronchitis in rats, and to explore its possible mechanism. Methods Forty SD rats were randomly divided into five groups, ie. a blank control group, amethylprednisolone control group, a model group, and two methylprednisolone intervention groups. Chronic bronchitis model was established by cigarette inhalation in the model group and two intervention groups. Methylprednisolone was injected intraperitoneally in the two intervention groups before exposing to cigarette smog ( at the dose of 1 mg/ kg and 10 mg/ kg, qd,respectively) . The protein expression of phosphodiesterase 4D ( PDE4D ) in trachea and lung samples was determined by immunohistochemical staining. The average optical density of positive staining of PDE4D was determined by image analysis technique and gray scale scanning. Bronchoalveolar lavage fluid ( BALF) was collected for total and differential cell counts, and the concentrations of TNF-αand interleukin-8 ( IL-8) in BALF were detected by ELISA. Results Cigarette smoking induced obvious airway inflammation in the
model group, and the inflammation was alleviated in the two methylprednisolone intervention groups.Compared with the two control groups, the expression of PDE4D was obviously elevated in tracheal and lungs in the model group( P lt; 0. 05) . Moreover, the increased expression of PDE4D was positively related with the
increased release of TNF-αand IL-8 in BALF. The expression of PDE4D and the release of TNF-αand IL-8 in BALF were decreased after the treatment with methylprednisolone in a dose-dependent manner ( P lt;0. 05) . Compare with the low dose intervention group, there was no markedly difference related to PMN
number and TNF-α release in the high dose intervention group ( P gt; 0.05) . Conclusions Methylprednisolone may alleviate airway inflammation of chronic bronchitis by inhibiting the expression of PDE4D in rats. Inhibition of PDE4D may down-regulate TNF-αactivity, which may further reduce IL-8 release and alleviate airway inflammation.

Citation： LI li,WANG Xiangdong.. Methylprednisolone Alleviates Airway Inflammation of Chronic Bronchitis by Inhibiting the Expression of Phosphodiesterase 4D in Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(6): 534-538. doi: Copy

1.	Sherrill DL, Holberg CJ, Enright PL, et al. Longitudinal analysis of the effects of smoking onset and cessation on pulmonary function.Am J Respir Crit Care Med, 1994, 149: 591-597.
2.	Tang HF, Song YH, Chen JC, et al. Upregulation of Phosphodiesterase-4 in the lung of allergic rats. Am JRespire Crit Care Med,2005, 171: 823-828.
3.	Aggarwal BB, Kohr WJ, Hass PE, et al. Human tumor necrosis factor: production, purification, and characferization. J Biol Chem,1985, 260: 2345-2354.
4.	童旭峰, 刘进, 管彩虹, 等. 用被动吸烟的方法建立慢性支气管炎大鼠模型及研究. 中华综合医学, 2002, 3: 484-485.
5.	Aaron SD, Angel JB, Lunan M, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2001 ,163: 349-355.
6.	廖秀清, 宋云熙, 王彦, 等. 西洛司特对COPD 患者PBMC 分泌IL-8 和TNF-α的影响. 第三军医大学学报, 2006, 28: 257-259.
7.	Crocker IC, Townley RG. Therapeutic potential of phosphodiesterase 4 inhibitors in allergic diseases. Drugs Today, 1999, 35: 519-535.
8.	Fan Chung K. Phosphodiesterase inhibitors in airways disease. Eur J Pharmacol, 2006, 533: 110-117.
9.	郑绪阳, 谢强敏, 杜晓刚, 等. 大鼠急性肺损伤模型肺组织中磷酸二酯酶4 活性的变化. 中国药理学通报, 2006, 22: 844-848.
10.	Jin SL, Conti M. Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses. Proc Natl Acad Sci USA, 2002, 99: 7628-7633.
11.	Hamamoto M, Suga M, Nakatani T, et al. Phosphodiesterase type 4 inhibitor prevents acute lung injury induced by cardiopulmonary bypass in a rat model. Eur J Cardiot horac Surg, 2004,25 : 833-838.
12.	Ouagued M, Chouly CA, Brinchault G, et al. The novel phosphodiesterase 4 inhibitor. CI-1044. inhibits LPS- induced TNF-α production in whole blood from COPD patients. Pulm Pharmacol Ther, 2005, 18: 49-54.

1. Sherrill DL, Holberg CJ, Enright PL, et al. Longitudinal analysis of the effects of smoking onset and cessation on pulmonary function.Am J Respir Crit Care Med, 1994, 149: 591-597.
2. Tang HF, Song YH, Chen JC, et al. Upregulation of Phosphodiesterase-4 in the lung of allergic rats. Am JRespire Crit Care Med,2005, 171: 823-828.
3. Aggarwal BB, Kohr WJ, Hass PE, et al. Human tumor necrosis factor: production, purification, and characferization. J Biol Chem,1985, 260: 2345-2354.
4. 童旭峰, 刘进, 管彩虹, 等. 用被动吸烟的方法建立慢性支气管炎大鼠模型及研究. 中华综合医学, 2002, 3: 484-485.
5. Aaron SD, Angel JB, Lunan M, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2001 ,163: 349-355.
6. 廖秀清, 宋云熙, 王彦, 等. 西洛司特对COPD 患者PBMC 分泌IL-8 和TNF-α的影响. 第三军医大学学报, 2006, 28: 257-259.
7. Crocker IC, Townley RG. Therapeutic potential of phosphodiesterase 4 inhibitors in allergic diseases. Drugs Today, 1999, 35: 519-535.
8. Fan Chung K. Phosphodiesterase inhibitors in airways disease. Eur J Pharmacol, 2006, 533: 110-117.
9. 郑绪阳, 谢强敏, 杜晓刚, 等. 大鼠急性肺损伤模型肺组织中磷酸二酯酶4 活性的变化. 中国药理学通报, 2006, 22: 844-848.
10. Jin SL, Conti M. Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses. Proc Natl Acad Sci USA, 2002, 99: 7628-7633.
11. Hamamoto M, Suga M, Nakatani T, et al. Phosphodiesterase type 4 inhibitor prevents acute lung injury induced by cardiopulmonary bypass in a rat model. Eur J Cardiot horac Surg, 2004,25 : 833-838.
12. Ouagued M, Chouly CA, Brinchault G, et al. The novel phosphodiesterase 4 inhibitor. CI-1044. inhibits LPS- induced TNF-α production in whole blood from COPD patients. Pulm Pharmacol Ther, 2005, 18: 49-54.

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