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Published on: December 16, 2021
Clostridium-Derived p-Cresyl Metabolites Induce Inflammation and Apoptosis in Biliary Epithelial Cells
Haiyan Yu1, Haiyan Fu1, Jiamin Xu1
1Department of Colorectal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
Objective:
Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease, and the effects of p-cresyl sulfate (PCS) and p-cresyl glucuronide (PCG) in PBC remain unclear. This study aimed to evaluate the pro-apoptotic and pro-inflammatory effects of PCS and PCG.
Methods:
Human intrahepatic biliary epithelial cells (HIBEpiCs) were treated with PCS or PCG, and apoptosis was assessed by flow cytometry. Female C57BL/6 mice received intraperitoneal PCS or PCG. Liver inflammation was evaluated by H&E staining, apoptosis-related proteins (caspase-3, Bax, Bcl-2) by Western blotting, and serum TGF-β and IFN-γ by ELISA.
Results:
PCS and PCG increased apoptosis in HIBEpiCs. In vivo, PCS and PCG treated mice displayed portal lymphocytic infiltration and elevated serum IFN-γ and TGF-β. Hepatic caspase-3 and Bax were upregulated, whereas Bcl-2 was downregulated in a time-dependent manner.
Conclusions:
PCS and PCG promote intrahepatic inflammation and BEC apoptosis, suggesting that gut microbial metabolites may contribute to hepatobiliary immune injury.
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