6. Nanomaterials and Pyroptosis Pyroptosis described the peculiar death of macrophages infected by Salmonella typhimurium [147]. Several other bacteria triggering this atypical cell death modality have been identified. Pyroptosis neither constitutes a macrophage-specific process nor a cell death subroutine that only results from bacterial infection. Pyroptotic cells can exhibit apoptotic and/or necrotic morphological features. The most distinctive biochemical feature of pyroptosis

Inhibitors,research,lifescience,medical is the early caspase-1 activation associated with the generation of pyrogenic mediators, such as Interleukin-1β (IL-1β) [38]. Recently, it has been shown that the exposure of macrophages (both a mouse macrophage cell line and primary human alveolar macrophages) to carbon black GW3965 molecular weight nanoparticles resulted in inflammasome activation as defined by cleavage of caspase-1 to its active form and downstream IL-1β release. The carbon black nanoparticles-induced cell death was identified as pyroptosis through the inhibition of Inhibitors,research,lifescience,medical caspase-1 and pyroptosis by specific pharmacological inhibitors. The authors showed that, in this setting, TiO2 particles did not induce pyroptosis or significantly activate the

inflammasome [148]. In contrast, it has been shown that nano-TiO2 and nano-SiO2, Inhibitors,research,lifescience,medical but not nano-ZnO (zinc oxide) and carbon nanotubes, induced inflammasome activation but not cell death in murine bone marrow-derived macrophages and human macrophages cell line. Although the caspase-1 cleavage and IL-1β release was induced, the inflammation caused by nanoparticles Inhibitors,research,lifescience,medical was largely caused by the biological effect of IL-1α [149]. This apparent discrepancy could be explained considering the different concentration and kind of nanomaterials used in these studies; moreover, it is possible that different macrophages perform differently in response to nanomaterials. Future studies should address this issue. However, the Inhibitors,research,lifescience,medical identification of pyroptosis as a cellular response to carbon nanoparticles exposure is novel and relates to health impacts

of carbon-based particulates. 7. Conclusions and Perspectives The continued expansion Annual Review of Pharmacology and Toxicology of the nanotechnology field requires a thorough understanding of the potential mechanisms of nanomaterial toxicity for proper safety assessment and identification of exposure biomarkers. With increasing research into nanomaterial safety, details on the biological effects of nanomaterials have begun to emerge. The nanomaterials intrinsic toxicity has been attributed to their physicochemical characteristics, that is, their smallness and the remarkably large surface area per unit mass and high surface reactivity. In fact, their type, composition and modifications, size, shape, and surface charge should be considered. However, the complex death paradigms may also be explained by activation of different death pathways in a context-dependent manner.