Role of NLR family pyrin domain-containing 3 inflammasome in the activation of pancreatic stellate cells

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-1 beta and IL-18 accompanied by the upregulation of alpha-SMA, Col I and FN expression. Moreover, MCC950 or NLPR3 siRNA decreased the expression of alpha-SMA, Col I, FN, TGF-beta 1 and p-Smad3. Furthermore, MCC950 reversed the LPS-induced upregulation of alpha-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-beta 1/Smad3 pathway.

Automated summary

Activation of the NLRP3 inflammasome is directly involved in the activation of Pancreatic stellate cells in vivo and in vitro, and inhibiting NLRP3 suppresses the activation of PSCs through the TGF-β1/Smad3 pathway.