FIGURE 3.

Ambient air pollution mediated effects and mechanisms induced in human CF bronchial epithelial cells. (A) Particulate matter effects. Particles are responsible for cellular death occurring either by necrosis or apoptosis. They are also responsible for inflammation, DNA damage and oxidative stress by inducing expression of typical genes involved in such responses—interleukin 8 and 6 (IL-8 and IL-6) for inflammation; histone H2A family member X (H2AFX) for DNA damage repair; superoxide dismutase (SOD1/2), heme oxygenase 1(HMOX-1), nuclear factor erythroid-derived 2-like 2 (NFE2L2) or peroxiredoxin (PRDX2) for antioxidant response. (B) Ozone effects. Ozone is directly cytotoxic for bronchial epithelial cells by disrupting tight junctions and epithelial integrity and by causing apoptosis. Promoting the JAK2-STAT1 pathway, ozone leads to pro-inflammatory cytokines secretion through NF-κB activation. CFTR expression is also downregulated leading to CFTR activity decrease and a CF-like phenotype. (C) Manufactured nanoparticles effects. Nanoparticles are internalized into bronchial epithelial cells provoking necrosis and inflammation. Co-exposure with ozone causes increase in intranuclear delivery of these nanoparticles.