Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways

Abstract

4Kantonsschule Frauenfeld, Frauenfeld, SwitzerlandCombustion-derived and manufactured nanoparticles (NPs) are known to provoke oxidative stress and inflammatory responses in human lung cells; therefore, they play an important role during the development of adverse health effects. As the lungs are composed of more than 40 different cell types, it is of particular interest to perform toxicological studies with co-cultures systems, rather than with monocultures of only one cell type, to gain a better understanding of complex cellular reactions upon exposure to toxic substances. Monocultures of A549 human epithelial lung cells, human monocyte-derived macrophages and monocyte-derived dendritic cells (MDDCs) as well as triple cell co-cultures consisting of all three cell types were exposed to combustion-derived NPs (diesel exhaust particles) and to manufactured NPs (titanium dioxide and single-walled carbon nanotubes). The penetration of particles into cells was analysed by transmission electron microscopy. The amount of intracellular reactive oxygen species (ROS), the total antioxidant capacity (TAC) and the production of tumour necrosis factor (TNF)-a and interleukin (IL)-8 were quantified. The results of the monocultures were summed with an adjustment for the number of each single cell type in the triple cell co-culture. All three particle types were found in all cell and culture types. The production of ROS was induced by all particle types in all cell cultures except in monocultures of MDDCs. The TAC and the ( pro-) inflammatory reactions were not statistically significantly increased by particle exposure in any of the cell cultures. Interestingly, in the triple cell co-cultures, the TAC and IL-8 concentrations were lower and the TNF-a concentrations were higher than the expected values calculated from the monocultures. The interplay of different lung cell types seems to substantially modulate the oxidative stress and the inflammatory responses after NP exposure.

Investigating the Interaction of Cellulose Nanofibers Derived from Cotton with a Sophisticated 3D Human Lung Cell Coculture

“…In contrast, however, a study in which different nanofiber (single-walled CNTs (SWCNTs)) and nano-objects (titanium dioxide (TiO 2 )) were assessed for their ability to stimulate pro-inflammatory cytokine/chemokine markers, as well as affect total antioxidant capacity (TAC) within the triple cell coculture. 30 It was reported that the in vitro model elicited a significant decrease (p < 0.05) in the TAC following SWCNTs exposure, while TiO 2 caused a significant increase (p < 0.05) in TAC of the triple cell coculture. Similar results were found for the pro-inflammatory cytokine TNF-α and chemokine IL-8, in contrast to the findings of ref 29.…”

Activation of Pulmonary Dendritic Cells and Th2-Type Inflammatory Responses on Instillation of Engineered, Environmental Diesel Emission Source or Ambient Air Pollutant Particles in vivo

“…However, it is likely that both the perturbation of epithelial cell barrier integrity and direct activation of DC are important in the elicitation of a proallergic innate immune response to 'environmental danger signals' since interdigitating DC are after all capable of sampling ambient PM via the tight junctions of pulmonary epithelia [35,52,[61][62][63][64] . It is also important to point out that it has been shown that relatively larger macromolecules (for example respirable coarse/fine ambient PM) may not overcome the integrity of the bronchial epithelial cell barrier and instead may be deposited and accumulated on the luminal surface of the epithelia where DC residing essentially underneath the epithelial barrier may directly capture those particles without affecting the integrity of the epithelia at all [26] .…”

Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro–in vivo gap

“…Since the lung is expected to be one antioxidant capacity and the cytokine excretion 205 . It can therefore be stated that the interplay between different cell types significantly modulates the oxidative stress levels and the inflammatory response, which are both known to be affected by NP exposure.…”