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Current Topics in Pharmacology   Volumes    Volume 10  Issue 2
Abstract
The dynamic role of pulmonary fibroblasts in the pathogenesis of lung fibrosis
Corinne A. E. Martin-Chouly, Stéphanie Guillot, Stéphane Jouneau, Sylvie Caulet-Maugendre, Philippe Delaval, Vincent Lagente
Pages: 77 - 87
Number of pages: 11
Current Topics in Pharmacology
Volume 10  Issue 2

Copyright © 2006 Research Trends. All rights reserved

ABSTRACT
 
Pulmonary fibrosis is a chronic progressive interstitial lung disease characterized by a poor prognosis and limited response to treatment. The events leading to fibrosis consist essentially as an acute lung inflammation following by a late progressive deposition of extracellular matrix proteins. Understanding the cellular and molecular mechanisms in the lung that ultimately leads to excessive pulmonary fibrotic conditions has concerned considerable research investigation. Pulmonary exposure to chemotherapeutic drugs, bleomycin or silicate, leads to pulmonary fibrosis in humans and have been used in animal to model these lung pathologies. The first phase is characterized by a recruitment of inflammatory cells, such as neutrophils and macrophages, the release of inflammatory cytokines and chemokines, and the secretion of matrix remodelling protease, namely the matrix metalloproteinases. The progression from the initial inflammatory reaction to the subsequent fibroproliferative manifestation highlighted that lung fibroblast is a key cell for the connective tissue remodelling which takes place during pulmonary fibrosis development. Fibroblasts are capable of remodelling connective tissue but also interact with epithelial cells and other connective tissue cells and may thus control such phenomena as chronic lung fibrosis progression. Furthermore anti-inflammatory and immunomodulatory drugs currently used in interstitial lung disease fail to provide clear therapeutic effect. This paradox coincides with a number of experimental findings demonstrating that inflammation is necessary but is only one component of many required to induce and maintain chronic fibrosis. In keeping with an evolving hypothesis that pulmonary fibrosis is an abnormal wound healing disease, the pulmonary fibroblast should represents a major target in the treatment of these diseases.
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