Enhancement of gelatinase activity during development of subepithelial fibrosis in a murine model of asthma

被引:19
作者
Corbel, M
Caulet-Maugendre, S
Germain, N
Lagente, V
Boichot, E
机构
[1] Univ Rennes 1, INSERM, U456, Fac Sci Pharmaceut & Biol, F-35043 Rennes, France
[2] CHR Pontchaillou, Rennes, France
关键词
fibrosis; metalloproteinase; mice; ovalbumin; subepithelial; tissue inhibitor of matrix metalloproteinase;
D O I
10.1046/j.1365-2222.2003.01581.x
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background Chronic asthma is characterized by inflammatory cell infiltration and tissue remodelling leading to subepithelial fibrosis. Metalloproteinases (MMPs) are involved in degradation of extracellular matrix in most chronic inflammatory diseases. Objective The aim of this study was to investigate the expression of MMPs in the development of inflammatory processes associated or not with the concomitant development of subepithelial fibrosis in an experimental model of asthma. Methods Sensitized BP2 mice were challenged with ovalbumin (OA) every 2 weeks during 8 months. Several mice were removed once a month and bronchoalveolar lavages (BAL) or lung biopsies were performed. Results Lung sections stained with picrosirius and hydroxyproline measurements showed a significant collagen deposition after 16 weeks of OA challenge, demonstrating the development of subepithelial fibrosis. Pulmonary inflammation was present from the first OA challenge and was consistent throughout the 8 months of the study. Moreover, an up-regulation and activation of MMP-9 and, to a less extent, MMP-2 were observed in BAL fluid from challenged mice. The level of tissue inhibitor of metalloproteinases (TIMP)-1 increased after 12 weeks of OA challenge vs. control mice. Conclusion This study reveals that a decrease in the activation of the MMP-9 due to the increase in TIMP-1, could contribute to excessive collagen deposition following repeated antigen challenge in sensitized mice.
引用
收藏
页码:696 / 704
页数:9
相关论文
共 48 条
[31]   Migration of eosinophils through basement membrane components in vitro: Role of matrix metalloproteinase-9 [J].
Okada, S ;
Kita, H ;
George, TJ ;
Gleich, GJ ;
Leiferman, KM .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1997, 17 (04) :519-528
[32]  
Pardo A, 1996, BRAZ J MED BIOL RES, V29, P1109
[33]   STIMULATION OF THE CHEMOTACTIC MIGRATION OF HUMAN-FIBROBLASTS BY TRANSFORMING GROWTH-FACTOR-BETA [J].
POSTLETHWAITE, AE ;
KESKIOJA, J ;
MOSES, HL ;
KANG, AH .
JOURNAL OF EXPERIMENTAL MEDICINE, 1987, 165 (01) :251-256
[34]  
RAGHOW R, 1991, CHEST, V99, P615
[35]   COLLAGEN-SYNTHESIS BY NORMAL AND FIBROTIC HUMAN-LUNG FIBROBLASTS AND THE EFFECT OF TRANSFORMING GROWTH FACTOR-BETA [J].
RAGHU, G ;
MASTA, S ;
MEYERS, D ;
NARAYANAN, AS .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1989, 140 (01) :95-100
[36]   A simplified method for the analysis of hydroxyproline in biological tissues [J].
Reddy, GK ;
Enwemeka, CS .
CLINICAL BIOCHEMISTRY, 1996, 29 (03) :225-229
[37]   PREDOMINANT TH2-LIKE BRONCHOALVEOLAR LYMPHOCYTE-T POPULATION IN ATOPIC ASTHMA [J].
ROBINSON, DS ;
HAMID, Q ;
YING, S ;
TSICOPOULOS, A ;
BARKANS, J ;
BENTLEY, AM ;
CORRIGAN, C ;
DURHAM, SR ;
KAY, AB .
NEW ENGLAND JOURNAL OF MEDICINE, 1992, 326 (05) :298-304
[38]   CYTOKINES .3. CYTOKINES IN ASTHMA [J].
ROBINSON, DS ;
DURHAM, SR ;
KAY, AB .
THORAX, 1993, 48 (08) :845-853
[39]  
ROCHE WR, 1989, LANCET, V1, P520
[40]  
Swiderski RE, 1998, AM J PATHOL, V152, P821