Authors: X. He, L. Wang, Y. Rojanasakul
Affilation: West Virginia University, United States
Pages: 158 - 161
Keywords: nano particles, ROS, lung fibrosis
Several reports have shown that single-walled carbon nano tubes (SWCNT) caused lung fibrosis in rodents. The molecular mechanisms that govern SWCNT lung toxicity remain largely unaddressed. Our results indicate that SWCNTs induced ROS and mitochondrial inner membrane depolarization in BEAS-2B, A549 and WI38-VA13 cells at sub-toxic doses. SWCNTs also stimulated the secretion of a panel of inflammatory cytokines and chemokines from macrophages (Raw264.7) by activating the canonical NF-B pathway. Finally, conditioned media from SWCNT-treated macrophages induced the BEAS-2B and WI38-VA 13 production of fibrogenic growth factors TGF-β1 and PDGF that function as paracrine signals to promote the transformation of bronchial epithelial cells and lung fibroblasts into myofibroblasts, a key molecular step in the development of lung fibrosis. These results demonstrated that SWCNTs elicit molecular signaling events involving oxidative damage, inflammatory cytokine production, TGF-β1/PDGF activation, and myofibroblast transformation, which potentially underlie fibrogenesis in human lungs by SWCNTs. This work provides a simple and rapid molecular mechanism-based toxicity assessment method that can be used for high throughput screening of inflammatory/fibrogenic toxicants in vitro.