Early and Late Changes of MMP-2 and MMP-9 in Bleomycin-Induced Pulmonary Fibrosis
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of pulmonary fibrosis. To understand the role of MMP-2 and MMP-9 in pulmonary fibrosis, we evaluated the sequential dynamic change and different cellular sources of the 2 MMPs along the time course and their differential expression in the bronchoalveolar lavage (BAL) fluid and in the lung parenchyma of the bleomycin-induced pulmonary fibrosis models in rats. Materials and Methods: The level of MMPs in BAL fluid of 54 bleomycin-treated rats was assessed by zymography from 1 to 28 days after intratracheal bleomycin instillation. The level of MMPs in lung parenchyma was evaluated by immunohistochemistry. Results: MMP-2 and MMP-9 were markedly increased in both the BAL fluid and in the lung parenchyma of the bleomycin-treated rats, especially in the early phase with the peak on the 4th day. The levels of both MMPs in the BAL fluid correlated generally well to those in lung parenchyma, although the level of MMP-9 in BAL fluid was higher than MMP-2. In the lung parenchyma, the 2 MMPs, in early stage, were predominantly expressed in the inflammatory cells. In late stage, type II pneumocytes and alveolar epithelial cells at the periphery of the fibrotic foci retained MMP expression, which was more prominent in the cells showing features of cellular injury and/or repair. Conclusion: In bleomycin-induced pulmonary fibrosis, MMP-2 and MMP-9 may play important roles, especially in the early phase. In the late stage, the MMP-2 and MMP-9 may play a role in the process of repair.
Abstract
Purpose: Matrix metalloproteinases (MMPs) have been implicated in the pathogenesis of pulmonary fibrosis. To understand the role of MMP-2 and MMP-9 in pulmonary fibrosis, we evaluated the sequential dynamic change and different cellular sources of the 2 MMPs along the time course and their differential expression in the bronchoalveolar lavage (BAL) fluid and in the lung parenchyma of the bleomycin-induced pulmonary fibrosis models in rats. Materials and Methods: The level of MMPs in BAL fluid of 54 bleomycin-treated rats was assessed by zymography from 1 to 28 days after intratracheal bleomycin instillation. The level of MMPs in lung parenchyma was evaluated by immunohistochemistry. Results: MMP-2 and MMP-9 were markedly increased in both the BAL fluid and in the lung parenchyma of the bleomycin-treated rats, especially in the early phase with the peak on the 4th day. The levels of both MMPs in the BAL fluid correlated generally well to those in lung parenchyma, although the level of MMP-9 in BAL fluid was higher than MMP-2. In the lung parenchyma, the 2 MMPs, in early stage, were predominantly expressed in the inflammatory cells. In late stage, type II pneumocytes and alveolar epithelial cells at the periphery of the fibrotic foci retained MMP expression, which was more prominent in the cells showing features of cellular injury and/or repair. Conclusion: In bleomycin-induced pulmonary fibrosis, MMP-2 and MMP-9 may play important roles, especially in the early phase. In the late stage, the MMP-2 and MMP-9 may play a role in the process of repair.
참고문헌 (46)
- Crouch E, "Pathobiology of pulmonary fibrosis", Am J Physiol, 259, pp.L159~L184 (1990)
- Murphy G, "The matrix metalloproteinases and their inhibitors", Am J Respir Cell Mol Biol, 7, pp.120~125 (1992)
- Hayashi T, "Immunohistochemical study of metalloproteinases and their tissue inhibitors in the lungs of patients with diffuse alveolar damage and idiopathic pulmonary fibrosis", Am J Pathol, 149, pp.1241~1256 (1996)
- Fukuda Y, "Localization of matrix metalloproteinases-1, -2, and -9 and tissue inhibitor of metalloproteinase-2 in interstitial lung diseases", Lab Invest, 78, pp.687~698 (1998)
- Suga M, "Characteristic elevation of matrix metalloproteinase activity in idiopathic interstitial pneumonias", Am J Respir Crit Care Med, 162, pp.1949~1956 (2000)
- Ohnishi K, "Matrix metalloproteinase-mediated extracellular matrix protein degradation in human pulmonary emphysema", Lab Invest, 78, pp.1077~1087 (1998)
- Segura-Valdez L, "Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD", Chest, 117, pp.684~694 (2000)
- Ferry G, "Activation of MMP-9 by neutrophil elastase in an in vivo model of acute lung injury", FEBS Lett, 402, pp.111~115 (1997)
- Lemjabbar H, "Overexpression of alveolar macrophage gelatinase B (MMP-9) in patients with idiopathic pulmonary fibrosis: effects of steroid and immunosuppressive treatment", Am J Respir Cell Mol Biol, 20, pp.903~913 (1999)
- Eickelberg O, "Extracellular matrix deposition by primary human lung fibroblasts in response to TGFbeta1 and TGF-beta3", Am J Physiol, 276, pp.L814~L824 (1999)
- Yao PM, "Cell-matrix interactions modulate 92-kD gelatinase expression by human bronchial epithelial cells", Am J Respir Cell Mol Biol, 18, pp.813~822 (1998)
- Gabazza EC, "Bleomycin-induced lung fibrosis: the authors should have used another method to induce pulmonary lesions resembling human idiopathic pulmonary fibrosis", Am J Respir Crit Care Med, 165, pp.845~846 (2002)
- Allred DC, "Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer", J Natl Cancer Inst, 85, pp.200~206 (1993)
- Laemmli UK, "Cleavage of structural proteins during the assembly of the head of bacteriophage T4", Nature, 227, pp.680~685 (1970)
- Nettesheim P, "Morphogenesis of alveolar bronchiolization", Lab Invest, 26, pp.210~219 (1972)
- Strieter RM, "Con: Inflammatory mechanisms are not a minor component of the pathogenesis of idiopathic pulmonary fibrosis", Am J Respir Crit Care Med, 165, pp.1206~1207 (2002)
- Selman M, "Idiopathic pulmonary fibrosis: prevailing and evolving hypotheses about its pathogenesis and implications for therapy", Ann Intern Med, 134, pp.136~151 (2001)
- Gauldie J, "A new direction in the pathogenesis of idiopathic pulmonary fibrosis?", Respir Res, 3, pp.1~ (2002)
- White ES, "Thannickal VJ. Pathogenetic mechanisms in usual interstitial pneumonia", idiopathic pulmonary fibrosis, 2003, pp.201, 343~354
- Bonniaud P, "Adenoviral gene transfer of connective tissue growth factor in the lung induces transient fibrosis", Am J Respir Crit Care Med, 168, pp.770~778 (2003)
- Kelly M, "Re-evaluation of fibrogenic cytokines in lung fibrosis", Curr Pharm Des, 9, pp.39~49 (2003)
- Corbel M, "Role of gelatinases MMP-2 and MMP-9 in tissue remodeling following acute lung injury", Braz J Med Biol Res, 33, pp.749~754 (2000)
- Pardo A, "Gelatinases A and B are up-regulated in rat lungs by subacute hyperoxia: pathogenetic implications", Am J Pathol, 153, pp.833~844 (1998)
- Oggionni T, "Time course of matrix metalloproteases and tissue inhibitors in bleomycin-induced pulmonary fibrosis", Eur J Histochem, 50, pp.317~325 (2006)
- Yaguchi T, "Immunohistochemical and gelatin zymography studies for matrix metalloproteinases in bleomycin-induced pulmonary fibrosis", Pathol Int, 48, pp.954~963 (1998)
- Kawamoto M, "Cell proliferation during the process of bleomycin-induced pulmonary fibrosis in rats", Acta Pathol Jpn, 40, pp.227~238 (1990)
- Kuhn C 3rd, "An immunohistochemical study of architectural remodeling and connective tissue synthesis in pulmonary fibrosis", Am Rev Respir Dis, 140, pp.1693~1703 (1989)
- Betsuyaku T, "Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin", Am J Pathol, 157, pp.525~535 (2000)
- Legrand C, "Airway epithelial cell migration dynamics. MMP-9 role in cell-extracellular matrix remodeling", J Cell Biol, 146, pp.517~529 (1999)
- Kunugi S, "Role of MMP-2 in alveolar epithelial cell repair after bleomycin administration in rabbits", Lab Invest, 81, pp.1309~1318 (2001)
- Smith RE, "TNF and IL-6 mediate MIP-1alpha expression in bleomycin- induced lung injury", J Leukoc Biol, 64, pp.528~536 (1998)
- Oikonomou N, "Soluble TNF mediates the transition from pulmonary inflammation to fibrosis", PLoS ONE, 1, pp.e108~ (2006)
- Beeh KM, "Sputum matrix metalloproteinase-9, tissue inhibitor of metalloprotinease- 1, and their molar ratio in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and healthy subjects", Respir Med, 97, pp.634~639 (2003)
- Chung KF, "Inflammatory mediators in chronic obstructive pulmonary disease", Curr Drug Targets Inflamm Allergy, 4, pp.619~625 (2005)
- John M, "Increased production of matrix metalloproteinase-2 in alveolar macrophages and regulation by interleukin-10 in patients with acute pulmonary sarcoidosis", Exp Lung Res, 28, pp.55~68 (2002)
- Sasaki M, "Differential regulation of metalloproteinase production, proliferation and chemotaxis of human lung fibroblasts by PDGF, interleukin-1beta and TNF-alpha", Mediators Inflamm, 9, pp.155~160 (2000)
- Broekelmann TJ, "Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis", Proc Natl Acad Sci U S A, 통권 : 88, pp.6642~6646 (1991)
- Bonniaud P, "TGF-beta and Smad3 signaling link inflammation to chronic fibrogenesis", J Immunol, 175, pp.5390~5395 (2005)
- Kasai H, "TGF-beta1 induces human alveolar epithelial to mesenchymal cell transition (EMT)", Respir Res, 6, pp.56~ (2005)
- Bergeron A, "Cytokine profiles in idiopathic pulmonary fibrosis suggest an important role for TGF-beta and IL-10", Eur Respir J, 22, pp.69~76 (2003)
- Kunkel SL, "Interleukin-8 (IL-8): the major neutrophil chemotactic factor in the lung", Exp Lung Res, 17, pp.17~23 (1991)
- Yang K, "TGF-betal transgenic mouse model of thoracic irradiation: modulation of MMP-2 and MMP-9 in the lung tissue", J Huazhong Univ Sci Technolog Med Sci, 26, pp.301~304 (2006)
- Denholm EM, "Alveolar macrophage secretion of a 92-kDa gelatinase in response to bleomycin", Am J Physiol, 265, pp.L581~L585 (1993)
- Choi KH, "The role of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in cryptogenic organizing pneumonia", Chest, 121, pp.1478~1485 (2002)
- Corbel M, "Inhibition of bleomycin-induced pulmonary fibrosis in mice by the matrix metalloproteinase inhibitor batimastat", J Pathol, 193, pp.538~545 (2001)
- Lanchou J, "Imbalance between matrix metalloproteinases (MMP-9 and MMP-2) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in acute respiratory distress syndrome patients", Crit Care Med, 31, pp.536~542 (2003)