Nanoparticles-induced apoptosis of human airway epithelium is mediated by proNGF/p75NTR signaling

ABSTRACTEnvironmental and occupational exposures to respirable ultrafine fractions of particulate matter (PM) have been implicated in the initiation and exacerbation of lung diseases. However, the precise mechanisms underlying production of cell damage and death attributed to nanoparticles (NP) on human airway epithelium are not fully understood. This study examined the role of neurotrophic pathways in NP-induced airway toxicity. Size and agglomeration of TiO2 nanoparticles (TiO2-NP) and fine (TiO2-FP) particles were measured by dynamic light scattering. Expression and signaling of key neurotrophic factors and receptors were assessed by real-time polymerase chain reaction, flow cytometry, immunostaining, and Western blot in various respiratory epithelial cells after exposure to TiO2-NP or TiO2-FP. Particle-induced cell death was measured by flow cytometry after annexin V/propidium iodide staining. The role of neurotrophin-dependent apoptotic pathways was analyzed with specific blocking antibodies or siRNA...