Synthesis Of The Model PM2.5 Library And Identification The Role Of NLRP3 Inflammasome Activation In PM_2.5-induced Lung Inflammation

With the global economic development and urbanization,Particulate Matter(PM)has become an important factor threatening human health in recent years.Fine particulate matter(PM2.5)is an air pollutant which has a large surface area and carries toxic substances.Long-term exposures to PM2.5 are linked to respiratory infections,chronic obstructive pulmonary disease,lung cancer and stroke.PM2.5 can directly adhere to the lower respiratory tract and lung lobe of the human body,disturbing the pulmonary immune system and inducing inflammation.PM2.5 contains complex mixtures of pollutants,and their compositions also vary with time and location.It has been found that fossil fuel combustion and biomass burning due to winter heating are one of the main causes of increased PM2.5 pollution.In addition,due to the emission of industrial waste gas and automobile exhaust gas,the content of heavy metals and organic compounds in PM2.5 is increased,such as Zn,Cu,Fe,Cr,Pb,As and TPAHs.These components exacerbates the health risks of PM2.5.PM2.5 could be enter lung and interact with pulmonary immune system through respiratory exposure.Inflammation is a crucial trigger for most PM2.5-induced diseases.The inflammasome play a key role in regulating inflammation and cell death.Activation or dysregulation of inflammasome can lead to the development of spontaneous inflammation or autoimmune diseases.It is reported that PM2.5 could induce inflammation by inducing macrophages to M1 phenotype or inhibiting macrophages to M2 phenotype.PM2.5 can mediate inflammation through oxidative stress or activation of inflammasome.However,because of the complexity of PM2.5 composition and it’s region-and time-dependence,very little is known about how different components contribute to PM2.5-induced inflammatory responses.To identify the key PM2.5 components that are responsible for NLRP3 inflammasome activation,we established a model PM2.5 library.We selected carbon nanoparticles and toxic components BaP,Cr,Pb,As to synthesize the model PM2.5 library.MH-S and THP-1 Dual cell were selected as cell models to detect IL-1β production,Caspase-1 activity,intracellular ROS,NLRP3 and ASC expression induced by model PM2.5 library.The results show that the model PM2.5 library and the real PM2.5 is consistent in contaminant content,DLS,zeta potential,cytotoxicity and secretion of IL-1β.In addition,we discovered that As-containing model PM2.5 particles caused more IL-1βsecretion and intracellular ROS.The As-containing model PM2.5 particles also caused Caspase-1 activation,NLRP3 and ASC expression.In this study,the As-containing model PM2.5 particles activates the NLRP3 inflammasome by up-regulating the level of intracellular ROS.This study provides a method to explore the biological effects and the identificate the key components in PM2.5.