PM2.5 exposure aggravates oligomeric amyloid beta-induced neuronal injury and promotes NLRP3 inflammasome activation in an in vitro model of Alzheimer’s disease

Bian-Rong Wang, Jian-Quan Shi, Nian-Nian Ge, Zhou Ou, You-Yong Tian, Teng Jiang, Jun-Shan Zhou, Jun Xu, Ying-Dong Zhang

Numerous studies suggested that PM2.5 exposure was associated with increased risk of Alzheimer's disease (AD). But the precise mechanisms by which PM2.5 contributed to AD pathogenesis have not been clarified. In the presence or absence of neurons, oligomeric amyloid beta (oAβ)-primed microglia were stimulated with PM2.5. Firstly, we determined the effects of PM2.5 exposure on neuronal injury and inflammation in neurons-microglia co-cultures. Then, we examined whether NLRP3 inflammasome activation was involved in PM2.5-induced inflammation. After that, we investigated whether PM2.5 exposure increased ROS level in oAβ-stimulated microglia. At last, we examined whether ROS and NLRP3 inflammasome activation was required for PM2.5-induced neuronal injury in neurons-microglia co-cultures. In the present study, we showed that PM2.5 exposure aggravated oAβ-induced neuronal injury and inflammation in neurons-microglia co-cultures via increasing IL-1β production. Further, PM2.5-induced IL-1β production in oAβ-stimulated microglia was possibly dependent on NLRP3 inflammasome activation. Meanwhile, PM2.5 exposure increased ROS level in oAβ-stimulated microglia. ROS was required for PM2.5-induced IL-1β production and NLRP3 inflammasome activation in oAβ-stimulated microglia. More importantly, ROS and NLRP3 inflammasome activation was required for PM2.5-induced neuronal injury in neurons-microglia co-cultures. For the first time, these results suggested that the effects of PM2.5 under AD context were possibly mediated by NLRP3 inflammasome activation, which was triggered by ROS. Taken together, these findings have deepened our understanding on the role of PM2.5 in AD pathogenesis.