RT Journal Article
SR Electronic
T1 Silica-induced inflammasome activation in vivo and uptake in vitro
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P1102
VO 44
IS Suppl 58
A1 Paul Peeters
A1 Karin Sanders
A1 Tim Perkins
A1 Gernot Rohde
A1 Emiel Wouters
A1 Dirk Taeger
A1 Beate Pesch
A1 Niki Reynaert
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P1102.abstract
AB Pneumoconiosis is a form of interstitial lung disease that is characterized by massive fibrosis and inflammation, which occurs after long-term inhalation of particulate matter. Silicosis is refractory to treatment and an important health problem. Inflammasome activation in vitro and in animal models of silicosis has been shown to be important in the disease process. Earlier, we demonstrated that silica is taken up by and initiates inflammasome activation in bronchial epithelial cells in vitro. Here we wanted to investigate if inflammasome activation occurs in epithelial lung tissue of miners who were diagnosed with silicosis versus non-silicosis, how silica particles are taken up in bronchial epithelial in vitro and by which mechanism. Lung tissue was available of 40 miners who were diagnosed with silicosis by pathologists were matched to 40 miners, where there was no visible silicotic fibrosis. They were matched on the basis of birth (+ / - 5 years), number of years (+ / - 5 years) and the cumulative quartz exposure (+ / - 5 mg/m3/years). By immunohistochemistry, lung tissue slides were stained for caspase-1, interleukin-1β and HMGB1. In vitro we used an in house method for labeling FITC to cristobalite silica in order to trace particles by confocal imaging. We observed elevated inflammasome activation in all miners irrespective of the presence of silicotic nodules. Live imaging revealed that particles are actively taken up by the cell within minutes and confocal imaging revealed uptake and cellular localization near the nucleus of the cell. Silica exposure is associated with inflammasome activation in human lung tissue. In vitro live and confocal imaging showed active silica uptake by lung epithelial cells.