title: Cysteine cathepsins and caspases in silicosis.
abstract: Silicosis is an occupational pneumoconiosis caused by inhalation of crystalline silica. It leads to the formation of fibrohyalin nodes that result in progressive fibrosis. Alternatively, emphysema may occur, with abnormal destruction of collagen fibres in the advanced stages. Although the pathophysiological mechanisms remain unclear, it has been established that the lung responds to silica by massive enrollment of alveolar macrophages, triggering an inflammatory cascade of reactions. An imbalance in the expression of lung proteases and their inhibitors is implicated in extracellular matrix remodelling and basement membrane disruption. Moreover, exposure to silica can initiate apoptotic cell death of macrophages. This review summarises the current knowledge on cysteine cathepsins that have been ignored so far during silicosis and outlines the recent progress on cellular pathways leading to silica-induced caspase activation, which have been partly delineated.
authors.affiliation: INSERM U618, Protéases et Vectorisation Pulmonaires, IFR 135 Imagerie Fonctionnelle, Université François Rabelais, F-37032 Tours, France. gilles.lalmanach@univ-tours.fr
authors.forename: Gilles
authors.initials: G
authors.lastname: Lalmanach
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Diot
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Godat
authors.forename: Fabien
authors.initials: F
authors.lastname: Lecaille
authors.forename: Virginie
authors.initials: V
authors.lastname: Hervé-Grépinet
mesh_terms: D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid; D020169:Caspases / Q000378:metabolism*; D002403:Cathepsins / Q000737:chemistry / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D012829:Silicosis / Q000201:enzymology*; D048069:Tumor Necrosis Factors / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors; D019014:fas Receptor; D002403:Cathepsins; D020169:Caspases; D003545:Cysteine