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          Institute: MPI für molekulare Genetik     Collection: Department of Computational Molecular Biology     Display Documents

ID: 446461.0, MPI für molekulare Genetik / Department of Computational Molecular Biology
Identification of novel transcriptional regulators involved in macrophage differentiation and activation in U937 cells.
Authors:Baek, Young-Sook; Haas, Stefan; Hackstein, Holger; Bein, Gregor; Hernandez-Santana, Maria; Lehrach, Hans; Sauer, Sascha; Seitz, Harald
Date of Publication (YYYY-MM-DD):2009-04-02
Title of Journal:BMC Immunology
Journal Abbrev.:BMC Immunology
Start Page:18
End Page:18
Copyright:2009 Baek et al; licensee 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.
Review Status:not specified
Audience:Experts Only
Abstract / Description:Background
Monocytes and macrophages play essential role in innate immunity. Understanding the underlying mechanism of macrophage differentiation and the identification of regulatory mechanisms will help to find new strategies to prevent their harmful effects in chronic inflammatory diseases and sepsis.
Maturation of blood monocytes into tissue macrophages and subsequent inflammatory response was mimicked in U937 cells of human histocytic lymphoma origin. Whole genome array analysis was employed to evaluate gene expression profile to identify underlying transcriptional networks implicated during the processes of differentiation and inflammation. In addition to already known transcription factors (i.e. MAFB, EGR, IRF, BCL6, NFkB, AP1, Nur77), gene expression analysis further revealed novel genes (i.e. MEF2, BRI, HLX, HDAC5, H2AV, TCF7L2, NFIL3) previously uncharacterized to be involved in the differentiation process. A total of 58 selected genes representing cytokines, chemokines, surface antigens, signaling molecules and transcription factors were validated by real time PCR and compared to primary monocyte-derived macrophages. Beside the verification of several new genes, the comparison reveals individual heterogeneity of blood donors.
Up regulation of MEF2 family, HDACs, and H2AV during cell differentiation and inflammation sheds new lights onto regulation events on transcriptional and epigenetic level controlling these processes. Data generated will serve as a source for further investigation of macrophages differentiation pathways and related biological responses.
Comment of the Author/Creator:corresponding author email: seitz@molgen.mpg.de
Harald Seitz

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2172/10/18
External Publication Status:published
Document Type:Article
Communicated by:Martin Vingron
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Institute of Clinical Immunology, University Hospital, 35392 Giessen, Germany;
2.Department of Rheumatology and Clinical Immunology, Charité University Medicine, 10117 Berlin, Germany.
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