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BMC Immunology
Published in: BMC Immunology 1/2009

Open Access 01-12-2009 | Research article

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

Authors: Young-Sook Baek, Stefan Haas, Holger Hackstein, Gregor Bein, Maria Hernandez-Santana, Hans Lehrach, Sascha Sauer, Harald Seitz

Published in: BMC Immunology | Issue 1/2009

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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.
Appendix
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Metadata
Title
Identification of novel transcriptional regulators involved in macrophage differentiation and activation in U937 cells
Authors
Young-Sook Baek
Stefan Haas
Holger Hackstein
Gregor Bein
Maria Hernandez-Santana
Hans Lehrach
Sascha Sauer
Harald Seitz
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2009
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/1471-2172-10-18

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