The Anti-inflammatory Effects of ProteasomeInhibitor MG-132 on Rats with Acute Lung Injury Induced by Lipopolysaccharide_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

MengWen ,  LiuZhaohui , FanWei , LiangZhike , CaiGuangping

Department of Respiratory Medicine, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 510180, China;

Corresponding author：

LiuZhaohui, Email: gz_zhaohui_liu@sina.com

Keywords：

Acute lung injury; MG-132; Intercellular cell adhesion molecule-1; Tumor necrosis factor-α; Nuclear factor-kappa B

DOI：

10.7507/1671-6205.2014090

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Abstract Full text Figures/Tables Video References Cited by

Objective To explore the anti-inflammatory mechanism of the proteasome inhibitor MG-132 on rats with acute lung injury (ALI). Methods 54 male SD rats were randomly divided into a control group,an ALI group,and a MG-132 group. LPS (5 mg/kg) was injected via tail vein in the ALI group and the MG-132 grouop,while the normal saline was given instead in the control group. MG-132 (10 mg/kg) was injected intraperitoneally at 30 min before LPS administration in the MG-132 group. Six rats in each group were sacrificed at 2,4,and 8h after normal saline or LPS administration. Then the following parameters were observed including pathology changes of lung tissue,wet to dry weight ratio of lung tissue (W/D),the levels of ICAM-1 and TNF-α in bronchoalveolar lavage fluid (BALF) by ELISA,and the protein level of nuclear factor-kappa B P65 (NF-κB P65) in lung tissue by Western blot. Results The pathological observation showed the typical ALI performance,as obvious pulmonary tissue congestion,edema,a large number of inflammatory cells infiltration in the ALI group. These inflammatory performance were obviously alleviated in the MG-132 group. Compared with the control group,the W/D,the levels of ICAM-1 and TNF-α in BALF,and the expression of the protein NF-κB P65 in lung tissue at 2,4 and 6h in the ALI group were significantly increased(P<0.05). Above parameters were significantly decreased in the MG-132 group compared with the ALI group. The expression of the protein NF-κB P65 was significantly positively related with the levels of ICAM-1 and TNF-α in BALF(P<0.01). Conclusion MG-132 can suppress inflammatory response in endotoxin-induced acute lung injury,which may be related to inhibition of NF-κB activation.

Citation： MengWen, LiuZhaohui, FanWei, LiangZhike, CaiGuangping. The Anti-inflammatory Effects of ProteasomeInhibitor MG-132 on Rats with Acute Lung Injury Induced by Lipopolysaccharide. Chinese Journal of Respiratory and Critical Care Medicine, 2014, 13(4): 370-373. doi: 10.7507/1671-6205.2014090 Copy

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1. Matthay MA,Zimmerman GA.Acute lung injury and the acute respiratory distress syndrome:four decades of inquiry into pathogenesis and rational management.Am J Respir Cell Mol Biol,2005,33:319-327.
2. Li G,Malinchoc M,Cartin-Ceba R,et al.Eight-year trend of acute respiratory distress syndrome:a population-based study in Olmsted County,Minnesota.Am J Respir Crit Care Med,201l,183:59-66.
3. Madjdpour L,Kneller S,Booy C,et al.Acid-induced lung injury:role of nuclear factor-kappa B.Anesthesiology,2003,99:1323-1332.
4. Duma D,Silva-Santos JE,Assreuy J.Inhibition of glucocorticoid receptor binding by nitric oxide in endotoxemic rats.Crit Care Med,2004,32:2304-2310.
5. Cao JL,He JH,Ding HL,et al.Activation of the spinal ERK signaling pathway contributes naloxone-precipitated withdrawal in morphine dependent rats.Pain,2005,118:336-349.
6. Johnson ER,Manhay MA.Acute lung injury:epidemiology,pathogenesis,and treatment.J Aerosol Med Pulm Drug Deliv,2010,23:243-252.
7. Sharif O,Bolshakov VN,Raines S,et al.Transcriptional profiling of the LPS induced NF-kappaB response in macrophages.BMC Immunol,2007,8:1.
8. Muller WA.Mechanisms of leukocyte transendothelial migration.Annu Rev Pathol,2011,6:323-344.
9. Tiruppathi C,Shimizu J,Miyawaki-Shimizu K,et al.Role of NF-Kb-dependent caveolin-1 expression in the mechanism of increased endothelial permeability induced by lipopolysaccharide.J Biol Chem,2008,283:4210-4218.
10. Perkins ND.Integrating cell-signalling pathways with NF-kappaB and IKK function.Nat Rev Mol Cell Biol,2007,8:49-62.
11. Kwon DJ,Bae YS,Ju SM,et al.Casuarinin suppresses TNF-α-induced ICAM-1 expression via blockade of NF-κB activation in HaCa T cells.Biochem Biophys Res Commun,2011,409:780-785.
12. Wyler E,Kaminska M,Coc YM,et al.Inhibition of NF-kappaB activation with designed ankyrin-repeat proteins targeting the ubiquitin-binding/oligomerization domain of NEMO.Protein Sci,2007,16:2013-2022.
13. Elliott PJ,Zollner TM,Boehncke WH.Proteasome inhibition:a new anti-inflammatory strategy.J Mol Med(Berl),2003,81:235-245.
14. Ma XZ,Bartczak A,Zhang J,et al.Proteasome inhibition in vivo promotes survival in a lethal murine model of severe acute respiratory syndrome.J Virol,2010,84:12419-12428.
15. Chen X,Li SL,Wu T,et al.Proteasome inhibitor ameliorates severe acute pancreatitis and associated lung injury of rats.World J Gastroenterol, 2008,14:3249-3253.

Chinese Journal of Respiratory and Critical Care Medicine

The Anti-inflammatory Effects of ProteasomeInhibitor MG-132 on Rats with Acute Lung Injury Induced by Lipopolysaccharide

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