Cell cooperation and role of the P2X₇ receptor in pulmonary inflammation induced by nanoparticles.
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| Abstract |
Macrophages and alveolar epithelial cells are the first targets of inhaled nanoparticles (NPs) reaching the alveoli. Mono- or co-cultures of lung epithelial (A549 or NCI-H441) and macrophage (THP-1) cell lines were used to study the cell cooperation and the involvement of the P2X₇ cell death receptor during the inflammation caused by SiO₂ and TiO₂ NPs. Here we show that, secretion of pro-inflammatory cytokines (IL-1β, IL-6 and IL-8) in response to NPs exposure was higher in co-cultures than in mono-cultures. A functional P2X₇ receptor was found in all the cell lines studied. Its involvement in IL-1β secretion in co-cultures was demonstrated using a specific antagonist, the brilliant blue G. Furthermore, mono and co-cultures exhibited distinct secretion patterns of pro-inflammatory cytokines in response to NPs exposure, and we provide the first evidence that the P2X₇ receptor is involved in the inflammation triggered by SiO₂ and TiO₂ NPs, by increasing IL-1β secretion, and likely through the inflammasome pathway. Altogether, our data indicate that cell co-cultures used in this study represent valid models to study the inflammatory mechanisms of NPs within the alveoli.
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| Authors | Samir Dekali, Ariane Divetain, Thierry Kortulewski, Justine Vanbaelinghem, Christelle Gamez, Françoise Rogerieux, Ghislaine Lacroix, Patrice Rat |
| Journal | Nanotoxicology (Nanotoxicology) Vol. 7 Issue 8 Pg. 1302-14 (Dec 2013) ISSN: 1743-5404 [Electronic] England |
| PMID | 23020093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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