The Role of Myeloid Differentiation Protein 2 in Acute Lung Injury Rats Induced by Lipopolysaccharide_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

REN Weiying ¹ , HUA Feng ² , JIN Jianjun ³ , ZENG Haiying ⁴ , ZHU Lei ²

Department of Pulmonary Medicine, Research Institute of Respiratory Disease, Fudan University, Zhongshan Hospital.Shanghai, 200032, ChinaCorresponding Author: ZHULei, E-mail: tfzhu@ 126. com;

Corresponding author：

Keywords：

Myeloid differentiation protein 2; Acute lung injury; Lipopolysaccharide; Alveolar macrophages

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Objective To explore the expression of myeloid differentiation protein2 ( MD-2) in rat lung and its role in acute lung injury ( ALI) induced by lipopolysaccharide ( LPS) . Methods Twenty male SD rats were randomly divided into a LPS group and a control group. The wet/dry ratios of lung tissues were measured and the histological changes of lung tissues were observed under microscope. Alveolar macrophages were collected from bronchial alveolar lavage fluid ( BALF) . The MD-2 mRNA and protein expressions were detected by RT-PCR, Western blot, and immunohistochemistry respectively. The MD2-siRNA oligo were transfected into NR8383 cells and 1 μg/mL LPS was used to stimulate the cells. The expressions of MD-2 mRNA and protein were detected by RT-PCR and Western blot. The levels of TNF-αin rat serum and cell culture supernatant were detected by ELISA. Results Compared with the control group, the expressions of MD-2 mRNA and protein in alveolar macrophages and lung tissue were elevated ( P lt;0. 01) , as well as the level of TNF-αin rat serum. The expressions of MD-2 mRNA and protein in NR8383 cell and the level of
TNF-αin supernatant increased obviously after LPS stimulation ( P lt;0. 01) . There were no changes of MD-2 mRNA and protein expressions and TNF-α of NR8383 cells treated by MD-2 siRNA with or without LPS stimulation ( P gt;0. 05) . Conclusions The expression of MD-2 in lung increases obviously after challengedby LPS. KnockdownMD-2 gene of NR8383 cell byMD-2 siRNA can inhibit TNF-αsecretion induced by LPS stimulation.MD-2 may play an important role in rat ALI induced by LPS.

Citation： REN Weiying,HUA Feng,JIN Jianjun,ZENG Haiying,ZHU Lei. The Role of Myeloid Differentiation Protein 2 in Acute Lung Injury Rats Induced by Lipopolysaccharide. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(6): 614-618. doi: Copy

1.	Resman N, Vasl J, Oblak A, et al. Essential roles of hydrophobic residues in both MD-2 and toll-like receptor 4 in activation by endotoxin. J Biol Chem, 2009, 284 : 15052-15060 .
2.	钱桂生. 在实践中提高对急性肺损伤和急性呼吸窘迫综合征新概念的认识. 中国呼吸与危重监护杂志, 2002 , 1: 199-201 .
3.	Baumgarten G, Knuefermann P, Wrigge H, et al. Role of Toll-like receptor 4 for the pathogenesis of acute lung injury in Gram-negative sepsis. Eur J Anaesthesiol, 2006 , 23: 1041-1048.
4.	Imai Y, Kaba K, Neely GG, et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell, 2008, 133: 235-249 .
5.	李琦, 钱桂生, 张青, 等. 不同剂量脂多糖对大鼠急性肺损伤效应的观察. 第三军医大学学报, 2004, 26: 871-873 .
6.	Oshikawa K, Sugiyama Y. Gene expression of Toll-like receptors and associated molecules induced by inflammatory stimuli in the primary alveolar macrophage. Bio Bio Res Com, 2003, 305 : 649-655.
7.	杜晓辉, 张永明, 李荣, 等. 性别差异对脓毒症大鼠肺组织Toll样受体4 及髓样分化蛋白-2 基因表达的影响. 中国危重病急救医学杂志, 2005, 17: 726-729.
8.	Everhart MB, Han W, Sherrill TP, et al. Duration and intensity of NF-κB activity determine the severity of endotoxin-induced acute lung injury. J Immunology, 2006, 176: 4995-5005.
9.	Viriyakosol S, Tobias PS, Kirkland TN, et al. Mutational analysis of membrane and soluble forms of human MD-2. J Biol Chem, 2006 ,281: 11955-11964.
10.	Jia HP, Kline JN, Penisten A, et al. Endotoxin responsiveness of human airway epithelia is limited by low expression of MD-2. Am J Physiol, 2004 , 287: L428-437.
11.	Lauer S, Kunde YA, Apodaca TA, et al. Soluble MD2 increases TLR4 levels on the epithelial cell surface. Cell Immunology, 2009 ,255: 8 -16 .
12.	李永旺, 张德明, 钱桂生, 等.MD2 在内毒素激活肺泡II 型上皮细胞中的表达及作用. 重庆医学, 2007, 36: 1582-1584.
13.	Gropper MA, Wiener-Kronish J. The epithelium in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care,2008, 14: 11 -15 .
14.	Togbe D, Schnyder-Candrian S, Schnyder B, et al. Toll-like receptor and tumour necrosis factor dependent endotoxin-induced acute lung injury. Int J Exp Path, 2007, 88: 387-391 .
15.	李洪霞, 张进川, 赵亚力, 等. 地塞米松对急性肺损伤大鼠炎症介质/抗炎介质表达的影响. 中国呼吸与危重监护杂志, 2005 ,4: 65-68.

1. Resman N, Vasl J, Oblak A, et al. Essential roles of hydrophobic residues in both MD-2 and toll-like receptor 4 in activation by endotoxin. J Biol Chem, 2009, 284 : 15052-15060 .
2. 钱桂生. 在实践中提高对急性肺损伤和急性呼吸窘迫综合征新概念的认识. 中国呼吸与危重监护杂志, 2002 , 1: 199-201 .
3. Baumgarten G, Knuefermann P, Wrigge H, et al. Role of Toll-like receptor 4 for the pathogenesis of acute lung injury in Gram-negative sepsis. Eur J Anaesthesiol, 2006 , 23: 1041-1048.
4. Imai Y, Kaba K, Neely GG, et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell, 2008, 133: 235-249 .
5. 李琦, 钱桂生, 张青, 等. 不同剂量脂多糖对大鼠急性肺损伤效应的观察. 第三军医大学学报, 2004, 26: 871-873 .
6. Oshikawa K, Sugiyama Y. Gene expression of Toll-like receptors and associated molecules induced by inflammatory stimuli in the primary alveolar macrophage. Bio Bio Res Com, 2003, 305 : 649-655.
7. 杜晓辉, 张永明, 李荣, 等. 性别差异对脓毒症大鼠肺组织Toll样受体4 及髓样分化蛋白-2 基因表达的影响. 中国危重病急救医学杂志, 2005, 17: 726-729.
8. Everhart MB, Han W, Sherrill TP, et al. Duration and intensity of NF-κB activity determine the severity of endotoxin-induced acute lung injury. J Immunology, 2006, 176: 4995-5005.
9. Viriyakosol S, Tobias PS, Kirkland TN, et al. Mutational analysis of membrane and soluble forms of human MD-2. J Biol Chem, 2006 ,281: 11955-11964.
10. Jia HP, Kline JN, Penisten A, et al. Endotoxin responsiveness of human airway epithelia is limited by low expression of MD-2. Am J Physiol, 2004 , 287: L428-437.
11. Lauer S, Kunde YA, Apodaca TA, et al. Soluble MD2 increases TLR4 levels on the epithelial cell surface. Cell Immunology, 2009 ,255: 8 -16 .
12. 李永旺, 张德明, 钱桂生, 等.MD2 在内毒素激活肺泡II 型上皮细胞中的表达及作用. 重庆医学, 2007, 36: 1582-1584.
13. Gropper MA, Wiener-Kronish J. The epithelium in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care,2008, 14: 11 -15 .
14. Togbe D, Schnyder-Candrian S, Schnyder B, et al. Toll-like receptor and tumour necrosis factor dependent endotoxin-induced acute lung injury. Int J Exp Path, 2007, 88: 387-391 .
15. 李洪霞, 张进川, 赵亚力, 等. 地塞米松对急性肺损伤大鼠炎症介质/抗炎介质表达的影响. 中国呼吸与危重监护杂志, 2005 ,4: 65-68.

Chinese Journal of Respiratory and Critical Care Medicine

The Role of Myeloid Differentiation Protein 2 in Acute Lung Injury Rats Induced by Lipopolysaccharide

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