Inhibitory effect of aspirin on the expression of MMP-9 and its mechanism in LPS-induced RAW264.7 cells

Abstract

Abstract: AIM: To investigate the effect of aspirin on the expression of MMP-9 and its mechanism in LPS-induced RAW264.7 cells.METHODS: The cytotoxic effect of aspirin on LPS-induced RAW264.7 cells was detected by MTT assay. MMP-9mRNA expression was detected by quantitative real-time PCR. The protein expression level of MMP-9, p38MAPK and Phospho-p38 (P-p38) were examined by western blotting. After the inhibition of p38MAPK pathway by specific inhibitor SB203580, the gene and protein expression of MMP-9 was measured by Quantitative real-time PCR and western blotting separately.RESULTS: The gene and protein expression of MMP-9 were inhibited by aspirin in dose-dependent manner.The protein expression of P-p38 was significantly inhibited by aspirin as compared with LPS treatment group. However, the protein expression of p38MAPK was not significantly different. The expression of MMP-9mRNA and protein were obviously decreased after inhibiting p38MAPK pathway.CONCLUSION: The results suggest that aspirin has potent anti-atherosclerotic action with inhibitory action on MMP-9 production by blocking p38MAPK pathway in LPS-induced RAW264.7 cells.

Key words: aspirin, matrix metalloproteinase, atherosclerosis, macrophage

CLC Number:

R965.2

ZHANG Ping, SHEN Chen-lin, LI Lin, ZHANG Wei, YAO Cheng-zeng, HUANG Xiao-hui. Inhibitory effect of aspirin on the expression of MMP-9 and its mechanism in LPS-induced RAW264.7 cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(4): 388-393.

References

[1] Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics--2013 update: a report from the American Heart Association[J]. Circulation,2013,127(1):e6-e245.
[2] Ross R. Atherosclerosis-an inflammatory disease [J].N Engl J Med, 1999, 340(2):115-126.
[3] Ferroni P, Basili S, Martini F, et al. Serum metalloproteinase 9 levels in patients with coronary artery disease: a novel marker of inflammation [J]. J Invest Med, 2003, 51(5):295-300.
[4] 薛洁, 华轶男, 顾振纶, 等.阿司匹林抑制兔动脉粥样斑块破裂及其机制研究[J].中国药理学通报, 2008,24(10): 1335 -1339.
[5] Cho A, Graves J, Reidy MA. Mitogen-Activated Protein Kinases Mediate Matrix Metalloproteinase-9 Expression in Vascular Smooth Muscle Cells [J]. Arterioscler Thromb Vasc Biol, 2000, 20(12): 2527-2532.
[6] Burger AM, Zhang X, Li H, et al. Down-regulation ofT1A12 /mac25, a novel insulin-like growth factor binding protein related gene, is associated with disease progression in breast carcinomas [J].Oncogene,1998,16(19):2459-2467.
[7] Porkka KP, Visakorpi T. Detection of differentially expressed genes in prostate cancer by combining suppression subtractive hybridization and cDNA library array [J]. J Pathol, 2001, 93(1): 73-79.
[8] Díez J. Emerging role of matrix metalloproteinases in the pathophysiology of cardiac diseases [J]. Eur J Clin Invest, 2002, 32(5): 291-294.
[9] Loftus IM, Naylor AR, Goodall S, et al. Stephen Goodall, BSc. Increased Matrix Metalloproteinase-9 Activity in Unstable Carotid Plaques A Potential Role in Acute Plaque Disruption [J]. Stroke, 2000, 31(1):40-47.
[10]Luttun A, Lutgens E, Manderveld A, et al. Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein e-deficient mice against atherosclerotic media destruction but differentially affects plaque growth [J]. Circulation, 2004, 109(11): 1408-1414.
[11]齐永,高江平,李琦, 等. 阿司匹林对基质金属蛋白酶9启动子活性影响[J].中国临床药理学与治疗学, 2005, 10(10): 1190 -1193.
[12]Murono S, Yoshizaki T, Sato H,et al. Aspirin Inhibits Tumor Cell Invasiveness Induced by Epstein-Barr virus Latent Membrane Protein 1 through Suppression of Matrix Metalloproteinase-9 Expression. Cancer Res, 2000, 60(9): 2555-2561.
[13]Li L, Liu H, Peng J, et al. Regulations of the key mediators in inflammation and atherosclerosis by Aspirin in human macrophages [J]. Lipids in Health and Disease, 2010,9:16.
[14]陈利巧, 芦靖, 魏国会,等. 阿司匹林抗动脉粥样硬化作用及机制[J]. 河北医药, 2009, 31(19):2539-2540.
[15]Ono K, Han JH. The p38 signal transduction pathway activation and function [J]. Cell Signal, 2000,12(1): 1-13.
[16]Redondo S, Ruiz E, Ramajo M, et al. Role of TGF-b1 and MAP Kinases in the antiproliferative Effect of Aspirin in Human Vascular Smooth Muscle Cells [J]. PLoS One, 2010, 5(3):e9800.
[17]Mehta JL, Chen J, Yu F, et al. Aspirin inhibits ox-LDL-mediated LOX-1 expression and metalloproteinase-1 in human coronary endothelial cells [J]. Cardiovascular Research, 2004, 64(2): 243- 249.
[18]Yiqin Y, Meilin X, Jie X, et al. Aspirin inhibits MMP-2 and MMP-9 expression and activity through PPARα/γ and TIMP-1-Mediated mechanisms in cultured mouse celiac macrophages[J].Inflammation, 2009, 32(4): 233-241.