1. Academic Validation
  2. Serum amyloid A3 is required for caerulein-induced acute pancreatitis through induction of RIP3-dependent necroptosis

Serum amyloid A3 is required for caerulein-induced acute pancreatitis through induction of RIP3-dependent necroptosis

  • Immunol Cell Biol. 2021 Jan;99(1):34-48. doi: 10.1111/imcb.12382.
Xinyi Yang 1 Runsheng Li 2 Lu Xu 1 Feng Qian 1 3 Lei Sun 1
Affiliations

Affiliations

  • 1 Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, PR China.
  • 2 Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, PR China.
  • 3 Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Anhui Province, Bengbu, 233003, PR China.
Abstract

Serum amyloid A (SAA) is an early and sensitive biomarker of inflammatory diseases, but its role in acute pancreatitis (AP) is still unclear. Here, we used a caerulein-induced mouse model to investigate the role of SAA in AP and other related inflammatory responses. In our study, we found that the expression of a specific SAA isoform, SAA3, was significantly elevated in a caerulein-induced AP animal model. In addition, SAA3-knockout (Saa3-/- ) mice showed lower serum levels of amylase and Lipase, tissue damage and proinflammatory cytokine production in the pancreas compared with those of wild-type mice in response to caerulein administration. AP-associated acute lung injury was also significantly attenuated in Saa3-/- mice. In our in vitro experiments, treatment with cholecystokinin and recombinant SAA3 significantly induced Necroptosis and cytokine production. Moreover, we found that the regulatory effect of SAA3 on acinar cell Necroptosis was through a receptor-interacting protein 3 (RIP3)-dependent manner. Collectively, our findings indicate that SAA3 is required for AP by inducing an RIP3-dependent Necroptosis pathway in acinar cells and is a potential drug target for AP.

Keywords

Acinar cell; RIP3; acute pancreatitis; necroptosis; serum amyloid A3.

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