Cell cooperation and role of the P2X7 receptor in pulmonary inflammation induced by nanoparticles. Issue 8 (December 2012)

• Record Type: Journal Article
• Authors: Dekali, Samir; Divetain, Ariane; Kortulewski, Thierry; Vanbaelinghem, Justine; Gamez, Christelle; Rogerieux, Françoise; Lacroix, Ghislaine; Rat, Patrice
• Is Part Of: Nanotoxicology. Volume 7:Issue 8(2013:Dec.)
• Page Start: 1302
• Page End: 1314
• Publication Date: 2012-12
• Subjects: Toxicology -- Periodicals; 615.9
• DOI: 10.3109/17435390.2012.735269
• Languages: English
• ISSNs: 1743-5390

Abstract

<abstract> <title>Abstract</title> <p>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.</p> </abstract>