Hepatocyte-specific S100a8 and S100a9 transgene expression in mice causes Cxcl1 induction and systemic neutrophil enrichment

Cell Communication and Signaling

Research

Arndt Vogel¹  Silke Marhenke¹  Christine Bauer²  Julia Németh²  Lars Wiechert²  Aurora De Ponti²  Tobias Pusterla²  Peter Angel²  Ursula Klingmüller³  Sandra Manthey³  Jochen Hess⁴ 

[1] Department of Hepatology, Medical School Hannover, Hannover, Germany;Division of Signal Transduction and Growth Control, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany;Division of Systems Biology of Signal Transduction, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany;Junior Group Molecular Mechanisms of Head and Neck Tumors, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany;Department of Otolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Heidelberg, Germany;

关键词: Calgranulins;    Calprotectin;    Hepatocytes;    Neutrophils;    Chemokines;    Immune cell mobilization;   

DOI  :  10.1186/1478-811X-10-40

 received in 2012-08-10, accepted in 2012-12-07,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundCalprotectin consists of the Ca2+-binding proteins S100a8 and S100a9 that are induced in epithelial cells in response to tissue damage and infection. Both proteins are also secreted by activated innate immune cells and numerous studies demonstrate their crucial role in pathological conditions of acute and chronic inflammation.ResultsHere, we established a conditional mouse model with simultaneous S100a8 and S100a9 transgene expression in hepatocytes (TgS100a8a9hep) under the control of doxycycline to unravel the role of epithelial-derived Calprotectin on tissue homeostasis and inflammation. TgS100a8a9hep mice displayed a significant enrichment of neutrophils in peripheral blood and tissues with high blood content. Interestingly, Cxcl1 transcription was significantly induced in the liver of TgS100a8a9hep mice and primary hepatocytes derived thereof as compared to Control mice, accompanied by an increase of Cxcl1 serum levels. However, expression of other chemokines with a known function in neutrophil mobilization from the bone marrow, e.g. Csf3 and Cxcl2, was not altered. Doxycycline treatment of TgS100a8a9hep mice reduced Cxcl1 expression in the liver and resulted in normal numbers of neutrophils.ConclusionIn summary, our data demonstrate for the first time that hepatocyte-specific S100a8 and S100a9 expression induces a systemic mobilization of neutrophils by a specific activation of Cxcl1 transcription in the liver.

【 授权许可】

Unknown   
© Wiechert et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.