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Open Access Highly Accessed Research article

Identification of novel transcriptional regulators involved in macrophage differentiation and activation in U937 cells

Young-Sook Baek1, Stefan Haas2, Holger Hackstein3, Gregor Bein3, Maria Hernandez-Santana4, Hans Lehrach1, Sascha Sauer1 and Harald Seitz1*

Author Affiliations

1 Department of Vertebrate Genomics, Max-Planck-Institute for Molecular Genetics, 14195 Berlin, Germany

2 Department of Computational Molecular Biology, Max-Planck-Institute for Molecular Genetics, 14195 Berlin, Germany

3 Institute of Clinical Immunology, University Hospital, 35392 Giessen, Germany

4 Department of Rheumatology and Clinical Immunology, Charité University Medicine, 10117 Berlin, Germany

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BMC Immunology 2009, 10:18  doi:10.1186/1471-2172-10-18

Published: 2 April 2009

Abstract

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.

Results

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.

Conclusion

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.