Toll-like receptor 2 deficiency alleviates acute pancreatitis by inactivating the NF-κB/NLRP3 pathway.

Abstract

The early aseptic immune response is the key factor leading to the aggravation of acute pancreatitis (AP). Toll-like receptor (TLR) 2 is an important member of the TLR family, but the role of TLR2 in AP remains to be investigated. In the present study, we found that TLR2 expression was significantly increased in AP patients. In a mouse model of cerulein-induced AP, TLR2 deficiency resulted in reduced inflammation, reduced infiltration of pancreatic neutrophils and macrophages, and decreased expression of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-17 and IL-18. In addition, transcriptomic analysis revealed that nod-like receptor family pyrin domain-containing 3 (NLRP3) expression was increased in AP, and there was a significant correlation between NLRP3 and TLR2. This study found that TLR2 deficiency can lead to a decrease in the activation of the NF-κB/NLRP3 signalling pathway, and the NLRP3 inhibitor MCC950 can alleviate AP in mice. Therefore, this study confirmed that TLR2 participates in the development of AP by activating the NF-κB/NLRP3 pathway. This study suggested that TLR2 might be a novel therapeutic target for AP.