title: Cell cooperation and role of the P2X₇ receptor in pulmonary inflammation induced by nanoparticles.
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.
authors.affiliation: INERIS (Institut National de l'Environnement industriel et des RISques), Unité de Toxicologie expérimentale , 60550 Verneuil-en-Halatte , France.
authors.forename: Samir
authors.initials: S
authors.lastname: Dekali
authors.forename: Ariane
authors.initials: A
authors.lastname: Divetain
authors.forename: Thierry
authors.initials: T
authors.lastname: Kortulewski
authors.forename: Justine
authors.initials: J
authors.lastname: Vanbaelinghem
authors.forename: Christelle
authors.initials: C
authors.lastname: Gamez
authors.forename: Françoise
authors.initials: F
authors.lastname: Rogerieux
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Lacroix
authors.forename: Patrice
authors.initials: P
authors.lastname: Rat
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes; D007249:Inflammation; D007378:Interleukins / Q000032:analysis / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D014025:Titanium / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D058847:Inflammasomes; D007378:Interleukins; D058486:Receptors, Purinergic P2X7; C009495:titanium dioxide; D014025:Titanium