Polystyrene nanoplastic exposure enhances LPS-induced lung inflammation in mice by inducing M1 polarization of macrophages via ROS/JAK/STAT signaling pathway

Abstract

Abstract 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.