IL-1β expression and processing in lung responses to inhaled particles
Institution: | Université Catholique de Louvain |
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Department: | Louvain Centre for Toxicology and Applied Pharmacology |
Year: | 2015 |
Record ID: | 1075367 |
Full text PDF: | http://hdl.handle.net/2078.1/156760 |
The main purpose of this experimental work was to better characterize the pathophysiological signals implicated in the development of particle-induced release of the pro-inflammatory interleukin (IL-) 1β and lung inflammation. In response to micro- and nanosilica particles, we found that the alarmin IL-1α is rapidly released from damaged alveolar macrophages and represents the main endogenous signal inducing the in vivo synthesis of inactive IL-1β precursor (pro-IL-1β). We also discovered that during macrophage shrinkage upon particle exposure, inflammasome engagement, subsequent IL-1β maturation and secretion depend on water efflux across aquaporins in mice. We conclude that IL-1α release from and cellular water movements in alveolar macrophages are crucial in the establishment of neutrophilic inflammation induced by particles in the lungs. These new findings suggest promising biomarkers and therapeutic targets in lung inflammatory diseases induced by micro- and nanosilica particles. (BIFA - Sciences biomédicales et pharmaceutiques) – UCL, 2015