Papers by Pierre-régis Burgel
Presse médicale (Paris, France : 1983), 2009
Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by permanent ... more Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by permanent and progressive airway obstruction. Cigarette smoking is the main cause responsible for COPD although only 15 to 25 % of smokers develop COPD. Mechanisms underlying COPD pathogenesis are not fully understood. Structural abnormalities in small airways (bronchioles < 2mm in diameter) are the main determinants of airway obstruction; obstruction of these bronchioles is related to increase in airway wall thickness (associated with peribronchiolar fibrosis) and to plugging by mucus exudates. Alveolar wall destruction (emphysema) also contributes to airway obstruction and to gas exchange abnormalities. Current knowledge related to molecular and cellular mechanisms responsible for these structural modifications are reviewed.
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European Respiratory Journal, 2010
Cystic fibrosis (CF) is due to mutations in the CF transmembrane conductance regulator gene CFTR.... more Cystic fibrosis (CF) is due to mutations in the CF transmembrane conductance regulator gene CFTR. CF is characterised by mucus dehydration, chronic bacterial infection and inflammation, and increased levels of cytosolic phospholipase A2α (cPLA2α) products in airways. We aimed to examine the role of cPLA2α in the modulation of mucus production and inflammation in CFTR-deficient mice and epithelial cells. Mucus production was assessed using histological analyses, immuno-histochemistry and MUC5AC ELISA. cPLA2α activation was measured using an enzymatic assay and lung inflammation determined by histological analyses and polymorphonuclear neutrophil counts in bronchoalveolar lavages. In lungs from Cftr(-/-) mice, lipopolysaccharide induced mucus overproduction and MUC5AC expression associated with an increased cPLA2α activity. Mucus overproduction was mimicked by instillation of the cPLA2α product arachidonic acid, and abolished by either a cPLA2α null mutation or pharmacological inhibition. An increased cPLA2α activity was observed in bronchial explants from CF patients. CFTR silencing induced cPLA2α activation and MUC5AC expression in bronchial human epithelial cells. This expression was enhanced by arachidonic acid and reduced by cPLA2α inhibition. However, inhibition of CFTR chloride transport function had no effect on MUC5AC expression. Reduction of CFTR expression increased cPLA2α activity. This led to an enhanced mucus production in airway epithelia independent of CFTR chloride transport function. cPLA2α represents a suitable new target for therapeutic intervention in CF.
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European respiratory review : an official journal of the European Respiratory Society, 2015
This article is the summary of a workshop, which took place in November 2013, on the roles of mic... more This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g. post-transplantation bronchiolitis obliterans). These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importa...
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Papers by Pierre-régis Burgel