Mechanisms Underlying the Fibrogenic Responses of Carbon Nanotubes

Abstract Carbon nanotubes (CNTs) are newly developed engineered nanomaterials with remarkable properties employed for a wide range of numerous commercial and industrial applications. However, CNT exposure in various settings is a significant concern as CNTs are readily inhaled into human lungs resulting in debilitating pulmonary responses, most notably fibrosis. Several rodent studies have demonstrated consistent adverse pulmonary effects including inflammation and granulomatous lesions leading to interstitial and subpleural fibrosis. Some of the crucial mechanistic steps involved during CNT-induced fibrosis range from generation of reactive oxygen species, inflammation, release of proinflammatory cytokines that initiate several intracellular cell signaling cascades, and expansion of the pool of myofibroblast via epithelial–mesenchymal transition. Furthermore, physicochemical properties of CNT including length and surface functionalization can influence their fibrogenic activity. The objective of this chapter is to review, summarize, and discuss major cellular and molecular mechanisms driving CNT-induced fibrogenesis.