SWCNT exposure of alveolar epithelial cells and macrophages induced OPN and TGF-beta1 response.
Waltz-MJ; Murray-AR; Kisin-E; Shvedova-AA
Toxicologist 2011 Mar; 120(Suppl 2):463
Exposure of the lung to carbonaceous nanoparticles: single walled carbon nanotubes (SWCNT) leads to the development of pulmonary fibrosis (PF) and induction of a network of pro-fibrotic/pro-inflammatory cytokines including TGF-beta1 and osteopontin (OPN). TGF-beta1 is involved in fibrotic remodeling including fibroblast differentiation and enhanced deposition of collagen in the extracellular matrix. As part of the inflammatory cascade, OPN acts as a chemoattractant to guide polymorphonuclear neutrophils (PMN) and macrophages (M Phi) to the area of insult/injury and is also involved in collagen deposition. Potential interactions between OPN and TGF-beta1 have not been investigated even though both cytokines have been shown to be upregulated in response to SWCNT. We hypothesize that OPN increase in response to SWCNT potentiate TGF-beta1 production in lung cells. To test our hypothesis two cell types, alveolar epithelial cells (MLE-15) and RAW 264.7 M Phi were treated with SWCNT (6 mu g/cm2 - 48 mu g/cm2, for 24 hours). Exposure of the cells to SWCNT resulted in significantly enhanced OPN released found in the incubation medium (39.1% for MLE-15 and 38.6% for RAW 264.7 M Phi vs. respective controls). Using an OPN antibody we demonstrated an inhibition of OPN production in response to SWCNT. Further studies are needed to evaluate interplay between OPN and TGF-beta1 and their role in SWCNT induced pulmonary fibrosis.
Biological-effects; Cell-biology; Cell-damage; Cellular-reactions; Cytotoxic-effects; Fibrogenicity; Fibrous-bodies; Immunotoxins; Lung-disorders; Lung-fibrosis; Lung-irritants; Lung-tissue; Molecular-biology; Nanotechnology; Particulates; Pulmonary-disorders; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Statistical-analysis; Tissue-disorders; Toxic-effects; Toxic-materials
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC