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- Title
Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis.
- Authors
Tran, Quang Trung; Sendler, Matthias; Wiese, Mats L.; Doller, Julia; Zierke, Lukas; Gischke, Marcel; Glaubitz, Juliane; Tran, Van Huy; Lalk, Michael; Bornscheuer, Uwe T.; Weiss, Frank Ulrich; Lerch, Markus M.; Aghdassi, Ali A.
- Abstract
Acute pancreatitis (AP) is a major, globally increasing gastrointestinal disease and a biliary origin is the most common cause. However, the effects of bile acids (BAs), given systemically, on the pancreas and on disease severity remains elusive. In this study, we have investigated the roles of different circulating BAs in animal models for AP to elucidate their impact on disease severity and the underlying pathomechanisms. BAs were incubated on isolated acini and AP was induced through repetitive injections of caerulein or L-arginine; pancreatic duct ligation (PDL); or combined biliopancreatic duct ligation (BPDL). Disease severity was assessed using biochemical and histological parameters. Serum cholecystokinin (CCK) concentrations were determined via enzyme immunoassay. The binding of the CCK1 receptor was measured using fluorescence-labeled CCK. In isolated acini, hydrophobic BAs mitigated the damaging effects of CCK. The same BAs further enhanced pancreatitis in L-arginine- and PDL-based pancreatitis, whereas they ameliorated pancreatic damage in the caerulein and BPDL models. Mechanistically, the binding affinity of the CCK1 receptor was significantly reduced by hydrophobic BAs. The hydrophobicity of BAs and the involvement of CCK seem to be relevant in the course of AP. Systemic BAs may affect the severity of AP by interfering with the CCK1 receptor.
- Subjects
BILE acids; PANCREATITIS; PANCREATIC diseases; PANCREATIC duct; ENZYME-linked immunosorbent assay; FARNESOID X receptor; MICE
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 21, p13592
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms232113592