Advances in mechanisms and signaling pathways of carbon nanotube toxicity

Abstract

Carbon nanotubes (CNT) have been developed into new materials with a variety of industrial and commercial applications. In contrast, the physicochemical properties of CNT at the nanoscale render them the potency to generate toxic effects. Indeed, the potential health impacts of CNT have drawn a great deal of attention in recent years, owing to their identified toxicological and pathological consequences including cytotoxicity, inflammation, fibrosis, genotoxicity, tumorigenesis, and immunotoxicity. Understanding the mechanisms by which CNT induce toxicity and pathology is thus urgently needed for accurate risk assessment of CNT exposure in humans, and for safe and responsible development and commercialization of nanotechnology. Here, we summarize and discuss recent advances in this area with a focus on the molecular interactions between CNT and mammalian systems, and the signaling pathways important for the development of CNT toxicity such as the NF-κB, NLRP3 inflammasome, TGF-β1, MAPK, and p53 signaling cascades. With the current mechanistic evidence summarized in this review, we expect to provide new insights into CNT toxicology at the molecular level and offer new clues to the prevention of health effects resulting from CNT exposure. Moreover, we disclose questions and issues that remain in this rapidly advancing field of nanotoxicology, which would facilitate ascertaining future research directions.

In vivo activation of a T helper 2-driven innate immune response in lung fibrosis induced by multi-walled carbon nanotubes

“…CNT are respirable and tend to accumulate in the lungs owing to their fiber-like shape and high biopersistence, attributes known to cause the fibrogenic and carcinogenic effects of inhaled particles and fibers (Dong and Ma 2015a). In animal studies, CNT behave as inflammogenic and fibrogenic agents in the lung parenchyma and pleural space in size, shape, and surface property-dependent manners (Donaldson et al 2010; Dong and Ma 2015a; Johnston et al 2010). The possibility that exposure to CNT can lead to lung fibrosing disease in humans has received a particular attention in occupational, environmental, and consumer product safety evaluation of nanoexposure.…”

Carbon nanotubes stimulate synovial inflammation by inducing systemic pro-inflammatory cytokines

“…[1][2][3][4] Meanwhile, numerous studies have documented the in vitro and in vivo toxicities of CNTs. [5][6][7][8][9] A number of toxicological effects of CNTs have been identified including inflammation, fibrosis, genotoxicity and immunotoxicity. 10,11 Despite this progress, continuous effort is warranted to gain more insights into the definitive adverse outcome pathways (AOPs) for nanomaterials with high exposure risk for human beings, and a validated framework for human health risk assessment upon CNTs has not been developed yet.…”

Common and distinct mechanisms of induced pulmonary fibrosis by particulate and soluble chemical fibrogenic agents

“…On the other hand, lung fibrosis induced by soluble chemicals, such as bleomycin and paraquat, is believed to be derived directly from damaging the alveolar and airway cells by the chemicals (Bus and Gibson 1984; Dong and Ma 2015; Husain and Kumar 2005; Moore and Hogaboam 2008; Morgan and Seaton 1995). Nonetheless, in both scenarios, the pulmonary lesions include an acute-phase response characterized by inflammatory infiltration and tissue damage, and chronic fibrosis development marked by interstitial fibrosis, granuloma formation, and scarring of the lungs.…”