title: Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis.
abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wan
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Guojian
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Xing
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Maochun
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Congying
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Wenqin
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: wangxingpeng@hotmail.com.
authors.forename: Xingpeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: huguoyongsh@sina.com.
authors.forename: Guoyong
authors.initials: G
authors.lastname: Hu
mesh_terms: D061354:Acinar Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002766:Cholecystokinin / Q000633:toxicity; D021984:Cyclophilin A / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D002766:Cholecystokinin; D021984:Cyclophilin A
keywords: Acute pancreatitis; Cyclophilin A; Inflammatory cytokines; Necrosis; Nuclear factor-κB