Serum amyloid A3 is required for caerulein-induced acute pancreatitis through induction of RIP3-dependent necroptosis
Xinyi Yang
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240 PR China
Equal contributors.
Search for more papers by this authorRunsheng Li
Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072 PR China
Equal contributors.
Search for more papers by this authorLu Xu
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240 PR China
Search for more papers by this authorCorresponding Author
Feng Qian
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240 PR China
Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Anhui Province, Bengbu, 233003 PR China
Correspondence
Lei Sun and Feng Qian, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
E-mail: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Lei Sun
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240 PR China
Correspondence
Lei Sun and Feng Qian, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
E-mail: [email protected] and [email protected]
Search for more papers by this authorXinyi Yang
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240 PR China
Equal contributors.
Search for more papers by this authorRunsheng Li
Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072 PR China
Equal contributors.
Search for more papers by this authorLu Xu
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240 PR China
Search for more papers by this authorCorresponding Author
Feng Qian
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240 PR China
Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Anhui Province, Bengbu, 233003 PR China
Correspondence
Lei Sun and Feng Qian, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
E-mail: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Lei Sun
Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240 PR China
Correspondence
Lei Sun and Feng Qian, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
E-mail: [email protected] and [email protected]
Search for more papers by this authorAbstract
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.
Conflict of Interest
The authors declare that they have no competing financial interests.
Supporting Information
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