Induction of Inflammasome-dependent Pyroptosis by Carbon Black Nanoparticles

Abstract

Inhalation of nanoparticles has been implicated in respiratory morbidity and mortality. In particular, carbon black nanoparticles are found in many different environmental exposures. Macrophages take up inhaled nanoparticles and respond via release of inflammatory mediators and in some cases cell death. Based on new data, we propose that exposure of macrophages (both a macrophage cell line and primary human alveolar macrophages) to carbon black nanoparticles induces pyroptosis, an inflammasome-dependent form of cell death. Exposure of macrophages to carbon black nanoparticles resulted in inflammasome activation as defined by cleavage of caspase 1 to its active form and downstream IL-1␤ release. The cell death that occurred with carbon black nanoparticle exposure was identified as pyroptosis by the protective effect of a caspase 1 inhibitor and a pyroptosis inhibitor. These data demonstrate that carbon black nanoparticle exposure activates caspase 1, increases IL-1␤ release after LPS priming, and induces the proinflammatory cell death, pyroptosis. The identification of pyroptosis as a cellular response to carbon nanoparticle exposure is novel and relates to environmental and health impacts of carbon-based particulates.Macrophages are critical regulators of local immune homeostasis. They are highly adaptive components of the innate immune system and respond in diverse ways to pathogens and other potential danger signals (1-3). In the lung, the alveolar macrophage is the first line of defense against environmental exposures. Alveolar macrophages phagocytose particulate matter, release inflammatory cytokines, and interact with other cells and molecules through the expression of surface receptors. One way in which an immune response is generated in alveolar macrophages is through the phagocytosis of deposited particles within the respiratory tract (4).The nanoparticle industry has expanded substantially in recent years. A variety of engineered carbon nanoparticles is used in consumer products such as car tires, rubber, and printer toner cartridges (5). Nanoparticles are also being used as novel means of drug delivery. Additionally, carbonaceous nanoparticles are present as an environmental contaminant. Combustion processes are a significant source of carbon nanoparticles. Elemental carbon-based nanoparticles with a diameter of less than 100 nm are a major part of diesel exhaust and ambient pollution (6).Particulate ambient pollution is known to cause adverse health effects in susceptible individuals and aggravates existing respiratory conditions such as asthma and chronic obstructive pulmonary disease (7). Even moderate levels of ambient air particulates are known to induce acute adverse health effects such as mortality in heart and lung diseases and chronic lung morbidity (8). Ultrafine particles are unique in their ability to bypass mucociliary clearance mechanisms and penetrate into deeper regions of the respiratory tract (9 -12). Although bulk elemental carbon is considered chemically inert (as in diamond and gra...

Uromodulin, Inflammasomes, and Pyroptosis

“…15,16 Consistent with the hypothesis advanced by Darisipudi et al of an injurious role of inflammasome activation by uromodulin, toxin-induced pyroptosis may promote tissue injury, as shown for the lung. 15 However, the role of pyroptosis in kidney injury or in sterile inflammation has not been well characterized.…”

Silver Nanoparticles Induce Degradation of the Endoplasmic Reticulum Stress Sensor Activating Transcription Factor-6 Leading to Activation of the NLRP-3 Inflammasome

“…Conversely to the NLRC-4 or the AIM-2, the NLRP-3 inflammasome is controlled by a priming step that requires de novo protein translation (35). Although carbon nanotubes and carbon black have also been reported to activate this inflam- masome in THP-1 and murine bone marrow-derived cells (20,46), the effect of AgNP on the inflammasome has never been reported. Herein, we show a cytotoxic and inflammatory role of AgNP 15 as evidenced by induction of pyroptotic cell death and IL-1␤ secretion.…”

Exposure to nickel oxide nanoparticles induces pulmonary inflammation through NLRP3 inflammasome activation in rats

“…The cell model has been applied to investigate NP-induced pulmonary toxicity and inflammasome activation. 45,46 This study has also shown that NiONPs induce active caspase-1 expression and IL-1β release in macrophages. Notably, knockdown of Nlrp3 completely abolishes caspase-1 activity and mature IL-1β release induced by NiONPs.…”