2. Academic Validation
  3. INT-777, a bile acid receptor agonist, extenuates pancreatic acinar cells necrosis in a mouse model of acute pancreatitis

INT-777, a bile acid receptor agonist, extenuates pancreatic acinar cells necrosis in a mouse model of acute pancreatitis

  • Biochem Biophys Res Commun. 2018 Sep 3;503(1):38-44. doi: 10.1016/j.bbrc.2018.05.120.
Baiqiang Li 1,  Na Yang 1,  Chuling Li 2,  Chuwei Li 3,  Kun Gao 4,  Xiaochun Xie 4,  Xiaowu Dong 4,  Jing Yang 1,  Qi Yang 1,  Zhihui Tong 1,  Guotao Lu 5,  Weiqin Li 6
Affiliations

Affiliations

  • 1 Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
  • 2 Department of Respiratory Medicine, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, China.
  • 3 College of Clinical Medicine Science, Chengdu Medical College, Chengdu, 610083, Sichuan, China.
  • 4 Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, China.
  • 5 Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China; Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China. Electronic address: [email protected].
  • 6 Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. Electronic address: [email protected].
PMID: 29859191 DOI: 10.1016/j.bbrc.2018.05.120
Abstract

Bile acids receptor TGR5 and its agonist INT-777, which has been found to be involved in the NLRP3 inflammasome pathway, play an important role in inflammatory diseases. However, the role of INT-777 in acute pancreatitis (AP) has not been reported. In this present study, we found that TGR5 was expressed in pancreatic tissue and increased after AP onset induced by caerulein and further evaluated the impact of INT-777 on the severity of AP. The results showed that INT-777 could reduce the severity of AP in mice, which was manifested as decreased pancreatic tissue damage as well as the decrease of serum enzymes (amylase and Lipase), pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and the expression of necrosis related proteins (RIP3 and p-MLKL). Furthermore, we found that INT-777 reduced the Reactive Oxygen Species (ROS) production in pancreatic acinar cells and inhibited the activation of NLRP3 inflammasome pathway. In conclusion, our data showed that INT-777 could protect pancreatic acinar cell against necrosis and reduce the severity of AP, which may be mediated by inhibiting ROS/NLRP3 inflammasome pathway.

Keywords

Acute pancreatitis; INT-777; NLRP3 inflammasome; Reactive oxygen species; TGR5.

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