Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310006, China; Hangzhou Institute of Digestive Disease, Hangzhou 310006, China.
The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China.
Int Immunopharmacol. 2023 Aug;121:110547. doi: 10.1016/j.intimp.2023.110547. Epub 2023 Jun 23.
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.
早期无菌性免疫反应是导致急性胰腺炎（AP）加重的关键因素。Toll 样受体（TLR）2 是 TLR 家族的重要成员，但 TLR2 在 AP 中的作用仍有待研究。本研究发现，AP 患者 TLR2 表达明显增加。在胆酸钠诱导的 AP 小鼠模型中，TLR2 缺陷导致炎症减轻，胰腺中性粒细胞和巨噬细胞浸润减少，促炎细胞因子如白细胞介素（IL）-1β、IL-6、IL-17 和 IL-18 的表达减少。此外，转录组分析显示，AP 中 NOD 样受体家族 pyrin 结构域包含 3（NLRP3）表达增加，NLRP3 与 TLR2 之间存在显著相关性。本研究发现 TLR2 缺陷可导致 NF-κB/NLRP3 信号通路激活减少，NLRP3 抑制剂 MCC950 可减轻小鼠的 AP。因此，本研究证实 TLR2 通过激活 NF-κB/NLRP3 通路参与 AP 的发生。本研究提示 TLR2 可能成为 AP 的一种新的治疗靶点。
