Effects of metalloproteinases-9 and tissue inhibitor of metalloproteinase on airway remodeling and the intervention effect of anti-RANTES antibody in rats with asthma

Abstract

Abstract: AIM: To observe the effects of anti-RANTES antibody on the expression of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) in the lung tissue of asthma model, and study the intervention mechanism.METHODS: 36 male rats were randomly divided into three groups:control group, asthma group, and anti-RANTES antibody treated group.The immunohistochemistry method was used for marking the MMP-9 and TIMP-1 in the lung histological section and the mean optical densities of MMP-9 and TIMP-1 were measured by multifunction color patho-image analysator.The level of RANTES was detected by ELISA.RESULTS: The expression of MMP-9 and TIMP-1 in asthma group were increased significantly than those in control group (P<0.05), and the ratio of MMP-9/TIMP-1 was decreased.The expression of MMP-9 and TIMP-1 in the anti-RANTES antibody treated group were decreased significantly than those of control group (P<0.05), and the ratio of MMP-9/TIMP-1 was revived gradually, and there were no statistical significance compare with that of control group (P>0.05).The pathology changes of airway inflammation, epithelial hyperplasia and collogen deposit were decreased significantly than those of asthma group.CONCLUSION: The anti-RANTES antibody leads to decreasing the expression of MMP-9 and TIMP-1 in the lung tissue of asthma rats and adjusts the balance of the MMP-9 and TIMP-1, interferes in matrix remodeling, and plays an important role in delaying development of asthma airway remodeling.

Key words: asthma, metalloproteinases-9(MMP-9), tissueinhibitorofmetalloproteinase(TIMP-1), airwayremodeling, anti-RANTESantibody

CLC Number:

R965.2

LIU Ya-li, ZHANG Li, JIN Hai-yan, AN Shu-hua. Effects of metalloproteinases-9 and tissue inhibitor of metalloproteinase on airway remodeling and the intervention effect of anti-RANTES antibody in rats with asthma[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(9): 985-990.

References

[1] Lambert E, Dasse E, Haye B, et al. TIMPs as multifacial proteins [J].Crit Rwv Oncol Hematol, 2004, 49(3):187-198.
[2] Hayakawa T.Multiple functions of tissue inhibitors of metalloproteinase(TIMPs):a new aspect involving osteoclastic bone resorption [J].J Bone Miner Metab, 2002, 20(1):1-13.
[3] Razzaque MS, Taguchi T.Cellular and molecular events leading to renal tubulo interstitial fibrosis [J].Med Electron Microsc, 2002, 35(2):68-80.
[4] Lee KS, Jin SM, Lee H, et al. Imbalnce bewteen matrix metalloproteinase-9 and tissue ihnibitor of metalloproteinase-1 in toluene disoeynate induced asthma [J].Clin EXP Allegry, 2004, 34(2):276-284.
[5] Hoshino M, Takehashi M, Takai Y, et al. Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and inhibitor of metalloproteinase-1 expression in asthma [J].J Allergy Clin Immunol, 1999, 104 (2pt1): 356-363.
[6] Ndukwu MN, Halyko AJ, Halayko AJ, et al. Bronehoalveolar lavage fluid from asthmatic subjeets is mitogenic for human airway smoothmusele [J].Am J Respir Crit Care Med, 1999, 160(5):2062-2066.
[7] Tanaka H, Miyazaki N, Oashi K, et al. Sputum matrix metallo-proteinase-9:Tissue inhibitor of metalloproteinase-1 ratio in acute asthma [J].J Clin Immunol, 2000, 105(5): 900-905.
[8] Vignola AM, Rieeobono L, Mirabella A, et al. Sputum metalloproteinase-9 tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis [J].Am J Respir Crit Care Med, 1998, 158(6):1945-1950.
[9] Kitayama J, Mackay CR, Ponath PD, et al. The CC chemokine receptor CCR3 participates in stimulation of eosinophil arrest oninflammatory endot helium in shear flow [J].J Clin Invest, 1998, 101(9):2017-2024.
[10] Fryer AA, Spiteri MA, Bianco A, et al. The-403 G→A promoter polymorphism in the RANTES gene is associated with atopy and asthma [J].Genes Immoun, 2000, 1(8): 509-514.
[11] Becker S, Reed W, Enderson FW, et al. RSV infection of human airway epithelial cells causes production of the beta2chemokine RANTES [J].Am J Phy siol, 1997, 272(3 Pt1):L512-520.
[12] Elsner J, Kapp A.Modulation of eosinophil effector functions: the potential role of monoclonal antibodies and chemokine receptor antagonists [J].Allergy Asthma Proc, 2000, 21(6):3452-3459.

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