Single-walled Carbon Nanotubes Induce Fibrogenic Response by Promoting Epithelial/Fibroblast-to-Myofibroblast Transition: An in vitro Molecular Toxicity Pathway Based Risk Assessment

摘要

Single-walled carbon nanotubes (SWCNT) are novel material with unique electronic and mechanical properties. Several reports have shown that pulmonary exposure to SWCNT caused pulmonary fibrosis in rodents, although the molecular mechanisms of SWCNT-induced pulmonary toxicity remain largely unaddressed. Here, we report that SWCNT exert multiple effects on human lung cells. First, SWCNT induced mitochondrial inner membrane potential depolarization and generate ROS in human bronchial epithelial BEAS-2B cells, alveolar type II A549 cells, and fibroblast WI38-VA13 cells at sub-toxic doses. Second, SWCNT induced fibrogenic cytokine TGF-1 in BEAS-2B and macrophage RAW264.7 cells. Third, conditioned media from SWCNT-treated macrophages promoted epithelial/fibroblast-to-myofibroblast transiition, a key molecular event in the pathogenesis of lung fibrosis. This work provides a simple and rapid method for mechanismbased risk assessment of nanomaterial fibrogenicity.