Circular RNA circBbs9 promotes PM_2.5-induced lung inflammation in mice via NLRP3 inflammasome activation

Fine particulate matter (PM_2.5) is one of the most important components of environmental pollutants, and is associated with pulmonary injury. However, the biological mechanisms of pulmonary damage caused by PM_2.5 are poorly defined, especially the molecular pathways related to inflammation. Following system exposure to PM_2.5 for 3 months in normal mice and in chronic obstructive pulmonary disease (COPD) model mice, it was found that PM_2.5 exposure increased the expression of IL-1β and IL-18 in lung tissues via NLRP3 activation, and these effects were more intense in COPD model mice. Circular RNA (circRNA) sequencing showed that the expression profiles of circRNAs were changed after PM_2.5 exposure, and the positive roles of circBbs9 in inflammation induced by PM_2.5 were verified. The circBbs9 knockdown alleviated PM_2.5-induced inflammation via NLRP3 inflammasome inactivation, as well as IL-1β and IL-18 inhibition in RAW264.7 cells, while overexpression of circBbs9 had the opposite effect. Bioinformatics and luciferase reporter assays showed that circBbs9 bound to microRNA-30e-5p (miR-30e-5p) and co-regulated the expression of Adar, a downstream target gene of miR-30e-5p. Taken together, these results revealed that PM_2.5 induced pulmonary inflammation through NLRP3 inflammasome activation regulated by the circBbs9-miR-30e-5p-Adar pathway. Our findings provide a new target, circBbs9, for the assessment of lung inflammation and COPD exacerbation induced by PM_2.5 exposure.