Multi Wall Carbon Nanotubes (MWCNT), a graphene based nanoparticle, possess unique physiochemical properties. Considered as a technological breakthrough, production of MWCNT is rapidly increasing worldwide but toxicity profile of the nanomaterials is not clearly understood. Among the adverse effects, CNT have been shown to induce (the development of unusual) interstitial lung fibrosis at physiologically relevant exposure (10ug/mouse); however, the underlying mechanism is not fully known. In this present study, we investigated important MWCNT-induced fibrogenic mediators using cultured lung cell systems. Human bronchial epithelial (BEAS-2B) cells, alveolar epithelial (A549) cells, and lung fibroblast (CRL1490) cells were treated with MWCNT. Viability of MWCNT-exposed cells was determined by cell counting and WST-1 assay. Fibrogenic mediators, including Fibroblast Growth Factor-2, Vascular Growth Factor, Transforming Growth Factor â1 (TGF-â1), and Platelet Derived Growth Factor-A, were analyzed using Western Blots and end point ELISA. Our results show that 1) MWCNT decreased cell viability of epithelial cells in a dose and time dependent manner, 2) MWCNT exposure induced secretion of fibrogenic mediators from lung epithelial cells and fibroblasts at physiologically relevant concentrations of 0.02 to 0.6 ug/cm2 and 3) MWCNT directly induced collagen production from lung fibroblasts. In conclusion, MWCNT induced fibrogenic mediators in cultured human lung epithelial cells and stimulated collagen production from fibroblasts. These data are consistent with in vivo observations. Therefore, the in-vitro cell culture systems can be used for mechanistic studies and screening tests for MWCNT and similar fibrogenic nanoparticles.
Biological-effects; Cell-biology; Cell-damage; Cell-growth; Cellular-reactions; Cytotoxic-effects; Cytotoxicity; Dose-response; Exposure-levels; Inhalation-studies; Lung; Lung-disease; Lung-disorders; Lung-function; Lung-irritants; Nanotechnology; Particulate-sampling-methods; Physiological-effects; Pulmonary-disorders; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Time-weighted-average-exposure; Toxic-effects
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC