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Studies have shown that fine particulate matter (PM 2.5) remains a significant problem in developing countries and plays a critical role in the onset and progression of respiratory illnesses. Circular RNAs (circRNAs) are involved in many pathophysiological processes,but their relationship to PM 2.5 pollution is largely unexplored. To elucidate the functional role of hsa_circ_0000992 in PM 2.5 -induced inflammation in a human bronchial epithelial cell line (16HBE) and to clarify whether the competing endogenous RNA (ceRNA) mechanism is involved in the interrelationships between hsa_circ_0000992 and hsa-miR-936 and the inflammatory signaling pathways. Detection of inflammatory factors in 16HBE cells exposed to PM 2.5 by RT-qPCR and ELISA.High throughput sequencing and bioinformatics analysis methods were used to screen circRNA.The bioinformatics analysis method western blotting and dual-luciferase reporter gene system were used to verify mechanisms associated with circRNA. PM 2.5 cause inflammation in the 16HBE cells. High throughput sequencing and RT-qPCR result revealed that the expression of hsa_circ_0000992 was markedly up-regulated in 16HBE exposed to PM 2.5. The binding sites between hsa_circ_0000992 and hsa-miR-936 was confirmed by dual-luciferase reporter gene system.Western blotting and RT-qPCR showed that hsa_circ_0000992 can interact with hsa-miR-936 to regulate AKT serine/threonine kinase 3(AKT3),thereby activating the PI3K/AKT pathway and ultimately promoting the expression of interleukin (IL)− 1β and IL-8. PM 2.5 can induce the inflammatory response in 16HBE cells by activating the PI3K/AKT pathway. The expression of hsa_circ_0000992 increased when PM 2.5 stimulated 16HBE cells,and the circRNA could then regulate the inflammatory response.Hsa_circ_0000992 regulates the hsa-miR-936/AKT3 axis through the ceRNA mechanism,thereby activating the PI3K/AKT signaling pathway,increasing the expression of cellular inflammatory factors,and promoting PM 2.5 -induced respiratory inflammation. • PM 2.5 exposure could induce the alteration of circRNA expression profiles. • Hsa-circ_0000992 was upregulated expression and could play a proinflammatory role in the process of inflammation. • Hsa-circ_0000992 through a ceRNA mechanism regulates the hsa-miR-936/AKT3 axis modulate the PM 2.5 -driven inflammation. [ABSTRACT FROM AUTHOR]

NLRP3 inflammasome activation plays an important role in the development of pancreatic fibrosis. However, it is unclear whether the activation of the NLRP3 inflammasome is directly involved in the activation of Pancreatic stellate cells (PSCs). The aim of this study was to investigate the role and mechanism of the NLRP3 inflammasome in the activation of PSCs. In vivo, a rat model of chronic pancreatitis (CP) was induced by intravenous injection of dibutyltin dichloride (DBTC). In vitro, rat primary PSCs were isolated from pancreatic tissues and incubated with the NLRP3 inflammasome activator LPS, the NLRP3 inhibitor MCC950, or NLRP3 siRNA. The results showed that the expression of NLRP3, pro-Caspase-1, Caspase-1 and IL-18 was increased in the rat model of CP and during PSCs activation. LPS increased the protein levels of NLRP3, ASC, Caspase-1, IL-1β and IL-18 accompanied by the upregulation of α-SMA, Col I and FN expression. Moreover, MCC950 or NLPR3 siRNA decreased the expression of α-SMA, Col I, FN, TGF-β1 and p-Smad3. Furthermore, MCC950 reversed the LPS-induced upregulation of α-SMA, FN and Col Ⅰ expression in PSCs. This study revealed that the NLRP3 inflammasome is directly involved in the activation of PSCs in vivo and in vitro. Inhibiting NLRP3 suppresses the activation of PSCs through the TGF-β1/Smad3 pathway. Proposed role of NLRP3 inflammasome activation involved in PSCs activation. The current study applied LPS stimulation to show the involvement of NLRP3 inflammasome pathway in the secretion of IL-1β and IL-18 from PSCs contributed to the activation and ECM deposition by TGF-β1-Smad3 pathway, suggesting that blockage of the NLRP3 inflammasome axis represents a potential therapeutic approach to pancreatic fibrosis. [Display omitted] • NLRP3 inflammasome was activated with the extension of activation time of PSCs. • LPS triggered PSCs activation through activating NLRP3 Inflammasome. • Inhibition of NLRP3 inflammasome mitigates the activation of PSCs. • NLRP3 inflammasome activates the TGF-β1/Smad3 signaling pathway in PSCs. [ABSTRACT FROM AUTHOR]