Polystyrene nanoplastics-induced lung apoptosis and ferroptosis via ROS-dependent endoplasmic reticulum stress.

It has been shown that exposure to nanoplastics (MNPs) through inhalation can induce pulmonary toxicity, but the toxicological mechanism of MNPs on the respiratory system remains unclear. Therefore, we explored the toxicological mechanism of exposure to polystyrene nanoplastics (PS-NPs) (0.05, 0.15, 0.2 mg/mL) on BEAS-2B cells. Results revealed that PS-NPs induce oxidative stress, increased apoptosis rate measured by flow cytometry, the key ferroptosis protein (GPX4 and FTH1) reduction, increased iron content, mitochondrial alterations, and increased malondialdehyde (MDA) level. Besides, consistent results were observed in mice exposed to PS-NPs (5 mg/kg/2d, 10 mg/kg/2d). Thus, we proved that PS-NPs induced cell death and lung damage through apoptosis and ferroptosis. In terms of mechanism, the elevation of the endoplasmic reticulum (ER) stress protein expression (IRE1α, PERK, XBP1S, and CHOP) revealed that PS-NPs induce lung damage by activating the two main ER stress pathways. Furthermore, the toxicological effects of PS-NPs observed in this study are attenuated by the ROS inhibitor N-acetylcysteine (NAC). Collectively, NPs-induced apoptosis and ferroptosis are attenuated by NAC via inhibiting the ROS-dependent ER stress in vitro and in vivo. This improves our understanding of the mechanism by which PS-NPs exposure leads to pulmonary injury and the potential protective effects of NAC.

Cadmium-induced pyroptosis is mediated by PERK/TXNIP/NLRP3 signaling in SH-SY5Y cells.

Cadmium (Cd) is a hypertoxic heavy metal that may be exposed to environmental pollutants by humans and animals. It can lead to cognitive disfunction, and is linked to neurodegenerative diseases. Cadmium reportedly can induce endoplasmic reticulum (ER) stress, but few studies have concentrated on it in nerve cells, and the connection between ER stress and neuroinflammation. In this study, in vitro experiments on SH-SY5Y neuroblastoma cells were carried out. We aimed at exploring whether Cd attributed to the cell pyroptosis and the role of PERK in promoting this form of cell damage which can induce strong inflammatory responses. Our results demonstrated that CdCl2 treatment induced excess reactive oxygen species (ROS) production, caused significant modifications in the expression of PERK and increased TXNIP, NLRP3, IL-1ß, IL-18, and caspase1 in SH-SY5Y cells. In addition, scavenging ROS with N-acetylcysteine or inhibiting the expression of PERK by using GSK2606414, rescued the SH-SY5Y cells from cadmium-induced pyroptosis. In conclusion, the results suggest that Cd induces pyroptotic death of SH-SY5Y cells through ER stress, and this may be the potential mechanism of Cd incurring neurological diseases.

Ambient ozone, and urban PM2.5 co-exposure, aggravate allergic asthma via transient receptor potential vanilloid 1-mediated neurogenic inflammation.

Allergic asthma is the most common pulmonary inflammatory disease, and epidemiological studies have revealed that PM2.5 or ambient ozone (O3) exposure contribute to the higher prevalence of allergic asthma. Current experimental evidence focus principally on the pathogenic effect of exposure to a single air pollutant, ignoring the possible synergistic effect of combined exposure to a mix of these pollutants, which is a more realistic scenario. In this study, allergic mice and a nociceptor antagonist were used to explore the mechanisms of co-exposure to these two important air pollutants. Compared with exposure to either PM2.5 or O3, combined exposure to both greatly aggravated allergic asthma in a dose dependent manner, including increased airway hyperresponsiveness, goblet cell metaplasia, more severe airway inflammation and higher oxidative stress levels. In addition, co-exposure in the allergic mice resulted in elevation of the expression of transient receptor potential vanilloid 1 (TRPV1), and of the production of substance P (SP), which exacerbated lung inflammation by neurogenic inflammation. TRPV1 antagonist (capsazepine, CPZ) treatment for the co-exposed allergic mice, markedly attenuated TRPV1 expression and SP release, and reduced airway inflammation and oxidative damage, further alleviating airway hyperresponsiveness. We conclude that neuro-immune interactions might be involved in PM2.5 and O3 co-exposure aggravated allergic asthma.