title: Cationic nanoparticles disrupt cellular signaling in a cholesterol dependent manner.
abstract: In this study, we investigate the interaction of charged polystyrene particles with respiratory epithelial cells. Experiments were designed to reveal the effect of cellular interaction with particles of varying size and charge and how such interactions could alter cytokine induced cellular processes. A549 cells, containing a stably transfected Interleukin-8 (IL-8) Luciferase promoter construct, were cultured in the presence of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) and polystyrene particles for 4.5h. Several endpoints were measured: IL-8 gene expression, IL-6 protein, IL-8 protein, and NF-кB translocation. At 4.5h, cellular viability was maintained for the particle exposed cells. Interestingly, we found that only the cationic nanoparticles have the ability to disrupt the TNF-α stimulated cellular signaling by reducing the IL-8 promoter activity, IL-6 and IL-8 protein. Cationic nanoparticles reduce these processes through interfering with NF-κB translocation. However, the activity of the cationic nanoparticles on the IL-8 promoter and NF-κB translocation is lost when cholesterol is depleted from A549 cells before particle exposure, which suggests that cationic nanoparticles rely on membrane cholesterol integrity to disrupt cellular signaling.
authors.affiliation: University of Rochester, NY 14642, United States.
authors.forename: Chia T
authors.initials: CT
authors.lastname: Thach
authors.forename: Jacob N
authors.initials: JN
authors.lastname: Finkelstein
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008560:Membrane Fluidity; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000633:toxicity*; D011137:Polystyrenes / Q000633:toxicity*; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D011137:Polystyrenes; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol