NLRP3 inflammasome activation determines the fibrogenic potential of PM_(2.5) air pollution particles in the lung

Airborne fine particulate matter(PM_(2.5))is known to cause respiratory inflammation such as chronic obstructive pulmonary disease and lung fibrosis.NLRP3 inflammasome activation has been implicated in these diseases;however,due to the complexity in PM_(2.5)compositions,it is difficult to differentiate the roles of the components in triggering this pathway.We collected eight real-life PM_(2.5)samples for a comparative analysis of their effects on NLRP3 inflammasome activation and lung fibrosis.In vitro assays showed that although the PM_(2.5)particles did not induce significant cytotoxicity at the dose range of 12.5to 100μg/m L,they induced potent TNF-αand IL-1βproduction in PMA differentiated THP-1 human macrophages and TGF-β1 production in BEAS-2B human bronchial epithelial cells.At the dose of 100μg/m L,PM_(2.5)induced NLRP3 inflammasome activation by inducing lysosomal damage and cathepsin B release,leading to IL-1βproduction.This was confirmed by using NLRP3-and ASC-deficient cells as well as a cathepsin B inhibitor,ca-074 ME.Administration of PM_(2.5)via oropharyngeal aspiration at 2 mg/kg induced significant TGF-β1 production in the bronchoalveolar lavage fluid and collagen deposition in the lung at 21days post-exposure,suggesting PM_(2.5)has the potential to induce pulmonary fibrosis.The ranking of in vitro IL-1βproduction correlates well with the in vivo total cell count,TGF-β1 production,and collagen deposition.In summary,we demonstrate that the PM_(2.5)is capable of inducing NLRP3 inflammasome activation,which triggers a series of cellular responses in the lung to induce fibrosis.

Environmental risk assessment of selected organic chemicals based on TOC test and QSAR estimation models

Environmental risks of organic chemicals have been greatly determined by their persistence,bioaccumulation, and toxicity（PBT） and physicochemical properties. Major regulations in different countries and regions identify chemicals according to their bioconcentration factor（BCF） and octanol–water partition coefficient（Kow）, which frequently displays a substantial correlation with the sediment sorption coefficient（Koc）. Half-life or degradability is crucial for the persistence evaluation of chemicals. Quantitative structure activity relationship（QSAR） estimation models are indispensable for predicting environmental fate and health effects in the absence of field-or laboratory-based data. In this study, 39 chemicals of high concern were chosen for half-life testing based on total organic carbon（TOC） degradation,and two widely accepted and highly used QSAR estimation models（i.e., EPI Suite and PBT Profiler） were adopted for environmental risk evaluation. The experimental results and estimated data, as well as the two model-based results were compared, based on the water solubility, Kow, Koc, BCF and half-life. Environmental risk assessment of the selected compounds was achieved by combining experimental data and estimation models. It was concluded that both EPI Suite and PBT Profiler were fairly accurate in measuring the physicochemical properties and degradation half-lives for water, soil, and sediment.However, the half-lives between the experimental and the estimated results were still not absolutely consistent. This suggests deficiencies of the prediction models in some ways, and the necessity to combine the experimental data and predicted results for the evaluation of environmental fate and risks of pollutants.