Enhancement of gelatinase activity during development of subepithelial fibrosis in a murine model of asthma.
Clin Exp Allergy
; 33(5): 696-704, 2003 May.
Article
en En
| MEDLINE
| ID: mdl-12752601
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fibrosis Pulmonar
/
Asma
/
Gelatinasas
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Clin Exp Allergy
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Reino Unido