Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 18, 2016; 8(8): 401-410
Published online Mar 18, 2016. doi: 10.4254/wjh.v8.i8.401
Role of interleukin-1 and its antagonism of hepatic stellate cell proliferation and liver fibrosis in the Abcb4-/- mouse model
Florian P Reiter, Ralf Wimmer, Lena Wottke, Renate Artmann, Jutta M Nagel, Manuel O Carranza, Doris Mayr, Christian Rust, Peter Fickert, Michael Trauner, Alexander L Gerbes, Simon Hohenester, Gerald U Denk
Florian P Reiter, Ralf Wimmer, Lena Wottke, Renate Artmann, Jutta M Nagel, Alexander L Gerbes, Simon Hohenester, Gerald U Denk, Department of Medicine II, Liver Center Munich, University of Munich, D-81377 Munich, Germany
Manuel O Carranza, Doris Mayr, Institute of Pathology, University of Munich, D-80337 Munich, Germany
Christian Rust, Department of Medicine I, Krankenhaus Barmherzige Brüder, D-80639 Munich, Germany
Peter Fickert, Research Unit for Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, A-8036 Graz, Austria
Michael Trauner, Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, A-1090 Vienna, Austria
Gerald U Denk, Transplant Center Munich of the University of Munich, D-81377 Munich, Germany
Author contributions: Reiter FP, Wimmer R, Rust C, Fickert P, Trauner M, Gerbes AL, Hohenester S and Denk GU designed the research; Wimmer R, Nagel JM, Wottke L and Artmann R performed the experiments; Carranza MO and Mayr D performed the histological examinations and imaging; Reiter FP, Wimmer R, Hohenester S and Denk GU analysed the data; Reiter FP, Hohenester S and Denk GU prepared the manuscript; all of the authors discussed and approved the manuscript.
Supported by The Münchener Medizinische Wochenschrift (MMW); B. Braun-Stiftung (to Reiter FP); the Deutsche Forschungsgemeinschaft (HO 4460/2-1 to Hohenester S and RU 742/6-1 to Rust C).
Institutional review board statement: This study includes no data or material from patients. We confirm that all of the required permissions for this study were obtained from our local authorities as mentioned in the Institutional animal care and use committee statement.
Institutional animal care and use committee statement: We confirm that the animals for our studies were kept according to the local regulations. All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Regierung von Oberbayern; protocol number No.: 55.2.1.54-2532-104-11. All of the institutional and national guidelines for the care and use of laboratory animals were followed.
Conflict-of-interest statement: All of the authors declare that they have no conflict of interest.
Data sharing statement: The technical appendix, statistical code, and dataset are available from the corresponding author at florian.reiter@med.uni-muenchen.de.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Florian P Reiter, MD, Department of Medicine II, Liver Center Munich, University of Munich, Marchioninistr. 15, D-81377 Munich, Germany. florian.reiter@med.uni-muenchen.de
Telephone: +49-89-440073129 Fax: +49-89-440078864
Received: June 11, 2015
Peer-review started: June 11, 2015
First decision: September 18, 2015
Revised: January 7, 2016
Accepted: March 7, 2016
Article in press: March 9, 2016
Published online: March 18, 2016
Processing time: 278 Days and 17.9 Hours
Core Tip

Core tip: Interleukin-1 (IL-1) critically participates in hepatic stellate cells (HSCs) pathophysiology and in the progression of liver injury to fibrosis. We found that fibrosis was more pronounced in female than in male ATP-binding cassette transporter b4-/- animals. This fibrosis was associated with higher IL-1β mRNA expression levels. We showed that IL-1β promoted the proliferation of murine HSCs and described an antifibrotic effect of the clinically approved IL-1 receptor antagonist Anakinra in vitro. Despite the promising antifibrotic effects in vitro, Anakinra failed to improve liver fibrosis in this preclinical primary sclerosing cholangitis model. Its potency in other models of liver injury and fibrosis remains to be determined.