Journal
IMMUNOLOGY AND CELL BIOLOGY
Volume 99, Issue 1, Pages 34-48Publisher
WILEY
DOI: 10.1111/imcb.12382
Keywords
Acinar cell; acute pancreatitis; necroptosis; RIP3; serum amyloid A3
Categories
Funding
- National Natural Science Foundation of China [81773741, 81973329, 81770633]
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Serum amyloid A (SAA) plays a critical role in acute pancreatitis (AP) by inducing necroptosis in acinar cells through a RIP3-dependent pathway, making it a potential drug target for AP treatment. In a caerulein-induced AP model, the specific SAA3 isoform was significantly increased, and SAA3-knockout mice displayed reduced pancreatic damage and inflammation, suggesting the importance of SAA3 in the development of AP.
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 inSaa3(-/-)mice. In ourin vitroexperiments, 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.
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