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Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis
- 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.
Author: | Quang Trung Tran, Matthias SendlerORCiD, Mats L. Wiese, Julia Doller, Lukas Zierke, Marcel Gischke, Juliane Glaubitz, Van Huy Tran, Michael LalkORCiD, Uwe T. BornscheuerORCiD, Frank Ulrich Weiss, Markus M. LerchORCiD, Ali A. AghdassiORCiD |
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URN: | urn:nbn:de:gbv:9-opus-77429 |
DOI: | https://doi.org/10.3390/ijms232113592 |
ISSN: | 1422-0067 |
Parent Title (English): | International Journal of Molecular Sciences |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of first Publication: | 2022/11/05 |
Release Date: | 2024/01/22 |
Tag: | CCK1R binding; acute pancreatitis; bile acids; hydrophobicity |
Volume: | 23 |
Issue: | 21 |
Article Number: | 13592 |
Page Number: | 18 |
Faculties: | Universitätsmedizin / Klinik und Poliklinik für Innere Medizin Abt. Gastroenterologie, Endokrinologie und Ernährungsmedizin |
Collections: | Artikel aus DFG-gefördertem Publikationsfonds |
Licence (German): | Creative Commons - Namensnennung |