Pulmonary fibrosis has an aggressive course and is usually fatal for an average of three to six years after the onset of symptoms. Pulmonary fibrosis is currently associated with airway inflammation and with deposition of extracellular matrix (ECM) components in the lung interstitium. Matrix metalloproteinases (MMPs) are a major group of proteinases known to regulate the ECM remodeling and so they are hypothesized to be important in the process of lung fibrosis. We have observed a dramatic collagen deposition in lung sections, following intranasal administration of bleomycin. Bleomycin also induced a dose-dependent increase in gelatinase (MMP-2 and MMP-9) activities, associated with the recruitment of inflammatory cells, in the bronchoalveolar lavage fluids. Significant change of respiratory parameters studied by whole body plethysmography was noted after intranasal instillation of bleomycin versus control mice, showing an important respiratory failure in treated mice. This study support a role for gelatinases in the development of bleomycin-induced pulmonary fibrosis. These led to the concept that modulation of mediators associated with airway remodeling including gelatinises may be of interest for the future treatment of acute lung injury and pulmonary fibrosis.
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