Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Sombetzki, M; Fuchs, CD; Fickert, P; Österreicher, CH; Mueller, M; Claudel, T; Loebermann, M; Engelmann, R; Langner, C; Sahin, E; Schwinge, D; Guenther, ND; Schramm, C; Mueller-Hilke, B; Reisinger, EC; Trauner, M.
24-nor-ursodeoxycholic acid ameliorates inflammatory response and liver fibrosis in a murine model of hepatic schistosomiasis.
J Hepatol. 2015; 62(4):871-878
Doi: 10.1016/j.jhep.2014.11.020
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Trauner Michael
- Co-authors Med Uni Graz
- Claudel Thierry
- Fickert Peter
- Langner Cord
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Intrahepatic granuloma formation and fibrosis characterize the pathological features of Schistosoma mansoni infection. Based on previously observed substantial anti-fibrotic effects of 24-nor-ursodeoxycholic acid (norUDCA) in Abcb4/Mdr2(-/-) mice with cholestatic liver injury and biliary fibrosis, we hypothesized that norUDCA improves inflammation-driven liver fibrosis in S. mansoni infection. Adult NMRI mice were infected with 50 S. mansoni cercariae and after 12 weeks received either norUDCA- or ursodeoxycholic acid (UDCA)-enriched diet (0.5% wt/wt) for 4 weeks. Bile acid effects on liver histology, serum biochemistry, key regulatory cytokines, hepatic hydroxyproline content as well as granuloma formation were compared to naive mice and infected controls. In addition, effects of norUDCA on primary T-cell activation/proliferation and maturation of the antigen-presenting-cells (dendritic cells, macrophages) were determined in vitro. UDCA as well as norUDCA attenuated the inflammatory response in livers of S. mansoni infected mice, but exclusively norUDCA changed cellular composition and reduced size of hepatic granulomas as well as TH2-mediated hepatic fibrosis in vivo. Moreover, norUDCA affected surface expression level of major histocompatibility complex (MHC) class II of macrophages and dendritic cells as well as activation/proliferation of T-lymphocytes in vitro, whereas UDCA had no effect. This study demonstrates pronounced anti-inflammatory and anti-fibrotic effects of norUDCA compared to UDCA in S. mansoni induced liver injury, and indicates that norUDCA directly represses antigen presentation of antigen presenting cells and subsequent T-cell activation in vitro. Therefore, norUDCA represents a promising drug for the treatment of this important cause of liver fibrosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cholagogues and Choleretics - metabolism Cholagogues and Choleretics - pharmacology
- Disease Models, Animal -
- Drug Monitoring -
- Granuloma - drug therapy Granuloma - immunology Granuloma - pathology
- Immunohistochemistry -
- Inflammation - drug therapy Inflammation - immunology Inflammation - pathology
- Liver Cirrhosis - drug therapy Liver Cirrhosis - etiology Liver Cirrhosis - immunology Liver Cirrhosis - pathology Liver Cirrhosis - physiopathology
- Lymphocyte Activation - drug effects
- Mice -
- Schistosomiasis mansoni - complications Schistosomiasis mansoni - immunology Schistosomiasis mansoni - pathology Schistosomiasis mansoni - physiopathology
- T-Lymphocytes - drug effects T-Lymphocytes - immunology
- Treatment Outcome -
- Ursodeoxycholic Acid - analogs & derivatives Ursodeoxycholic Acid - metabolism Ursodeoxycholic Acid - pharmacology
- Find related publications in this database (Keywords)
- Liver fibrosis
- Bile acids
- Schistosoma mansoni infection
- Hepatic granulomas
- Anti-inflammatory/anti-fibrotic therapy