title: Cytokine production by co-cultures exposed to monodisperse amorphous silica nanoparticles: the role of size and surface area.
abstract: The aim of this study was to test the influence of nanoparticle size and surface area (SA) on cytokine secretion by co-cultures of pulmonary epithelial cells (A549), macrophages (differentiated THP-1 cells) and endothelium cells (EA.hy926) in a two-compartment system. We used monodisperse amorphous silica nanoparticles (2, 16, 60 and 104 nm) at concentrations of 5 μg/cm² cell culture SA or 10 cm² particle SA/cm². A549 and THP-1 cells were exposed to nanoparticles for 24h, in the presence of EA.hy926 cells cultured in an insert introduced above the bi-culture after 12h. Supernatants from both compartments were recovered and TNF-α, IL-6, IL-8 and MIP-1α were measured. Significant secretion of all cytokines was observed for the 2 nm particles at both concentrations and in both compartments. Larger particles of 60 nm induced significant cytokine secretion at the dose of 10 cm² particle SA/cm². The use of multiple cellular types showed that cytokine secretion in single cell cultures is amplified or mitigated in co-cultures. The release of pro-inflammatory mediators by endothelial cells not directly exposed to nanoparticles indicates a possible endothelium activation after inhalation of silica particles. This work shows the role of size and SA in cellular response to amorphous nanosilica.
authors.affiliation: Laboratory of Pneumology, Research Unit for Lung Toxicology, K.U. Leuven, Herestraat 49, Leuven 3000, Belgium.
authors.forename: Dorota
authors.initials: D
authors.lastname: Napierska
authors.forename: Leen C J
authors.initials: LC
authors.lastname: Thomassen
authors.forename: Bart
authors.initials: B
authors.lastname: Vanaudenaerde
authors.forename: Katrien
authors.initials: K
authors.lastname: Luyts
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
authors.forename: Johan A
authors.initials: JA
authors.lastname: Martens
authors.forename: Benoit
authors.initials: B
authors.lastname: Nemery
authors.forename: Peter H M
authors.initials: PH
authors.lastname: Hoet
mesh_terms: D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D016207:Cytokines; D012822:Silicon Dioxide