Nanoplastics (NPs) pollution poses a huge threat to the ecosystem and has become one of the environmental pollutants that have attracted much attention. There is increasing evidence that both oxidative stress and endoplasmic reticulum stress (ERS) are associated with polystyrene nanoplastics (PS‐NPs) exposure. Lipopolysaccharide (LPS) has been shown to induce apoptotic damage in various tissues, but whether PS‐NPs can aggravate LPS‐induced apoptosis in mouse kidneys through oxidative stress‐regulated inositol‐requiring enzyme 1 (IRE1)/X‐box binding protein 1 (XBP1) ERS pathway remains unclear. In this study, based on the establishment of in vitro and in vivo PS‐NPs and LPS exposure models alone and in combination in mice and HEK293 cells, the effects and mechanisms of PS‐NPs on LPS‐induced renal cell apoptosis were investigated. The results showed that PS‐NPs could aggravate LPS‐induced apoptosis. PS‐NPs/LPS can induce ERS through oxidative stress, activate the IRE1/XBP1 pathway, and promote the expression of apoptosis markers (Caspase‐3 and Caspase‐12). Kidney oxidative stress, ERS, and apoptosis in PS‐NPs + LPS combined exposure group were more severe than those in the single exposure group. Interestingly, 4‐phenylbutyric acid‐treated HEK293 cells inhibited the expression of the IRE1/XBP1 ERS pathway and apoptotic factors in the PS‐NPs + LPS combined exposure group. N‐acetyl‐L‐cysteine effectively blocked the activation of the IRE1/XBP1 ERS pathway, suggesting that PS‐NPs‐induced oxidative stress is an early event that triggers ERS. Collectively, these results confirmed that PS‐NPs aggravated LPS‐induced apoptosis through the oxidative stress‐induced IRE1/XBP1 ERS pathway. Our study provides new insights into the health threats of PS‐NPs exposed to mammals and humans.
Nanoplastics (NPs) are an emerging environmental pollutant. NPs can spike various tissues results to oxidative stress and tissue damage in organisms. While recent studies have reported a relationship between nanoparticles and respiratory system injury, the specific mechanism of NP exposure-induced lung damage remains to be explored. In the present study, C57BL6 male mice were treated intraperitoneal injection of PS-NPs and/or LPS. The relevant indicators were detected by HE staining, western blotting and qRT-PCR. RAW264.7 was pretreated with JAK2 inhibitor (AG490) to verify whether the JAK2/STAT3 signaling pathway is involved in PS-NPs exposure enhances LPS-induced pulmonary inflammatory response. We found decreased antioxidant capacity in mice lungs, activation of the JAK2/STAT3 pathway, and the expression levels of macrophage M1 marker genes increased (including CD16, CD86, and MCP1), while macrophage M2 marker genes (including CD206, PPARγ, and Arg1) expression levels decreased, resulting in a macrophage M1/M2 imbalance. In addition, PS-NPs can increase the expression of inflammation-related factors IL-1β, TNF-α and IL-6. In in vitro experiments, we obtained similar results to in vivo experiments. More importantly, the JAK2 pathway inhibitor AG490 reversed ROS-induced changes in macrophage imbalance and inflammation in PS-NPs and LPS-exposed RAW264.7 cells. In conclusion, PS-NPs activated the ROS/JAK/STAT pathway, aggravated LPS-induced lung M1/M2 macrophage imbalance and promoted inflammatory responses. Our results enrich the toxic effects and related molecular mechanisms of NPs-induced lung inflammation, and provide new insights into the toxic effects of NPs on mammals.
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