LPS regulates a set of genes in primary murine macrophages by antagonising CSF-1 action

Sester, D. P., Trieu, A., Brion, K., Schroder, K., Ravasi, T., Robinson, J. A., McDonald, R. C., Ripoll, V., Wells, C. A., Suzuki, H., Hayashizaki, Y., Stacey, K. J., Hume, D. A. and Sweet, M. J. (2005) LPS regulates a set of genes in primary murine macrophages by antagonising CSF-1 action. Immunobiology, 210 2-4: 97-107. doi:10.1016/j.imbio.2005.05.004

Author Sester, D. P.
Trieu, A.
Brion, K.
Schroder, K.
Ravasi, T.
Robinson, J. A.
McDonald, R. C.
Ripoll, V.
Wells, C. A.
Suzuki, H.
Hayashizaki, Y.
Stacey, K. J.
Hume, D. A.
Sweet, M. J.
Title LPS regulates a set of genes in primary murine macrophages by antagonising CSF-1 action
Journal name Immunobiology   Check publisher's open access policy
ISSN 0171-2985
Publication date 2005
Sub-type Article (original research)
DOI 10.1016/j.imbio.2005.05.004
Volume 210
Issue 2-4
Start page 97
End page 107
Total pages 11
Place of publication Jena
Publisher Urban & Fischer Verlag
Collection year 2005
Language eng
Subject C1
320202 Cellular Immunology
730102 Immune system and allergy
Abstract We previously reported that bacterial products such as LPS and CpG DNA down-modulated cell surface levels of the Colony Stimulating Factor (CSF)-1 receptor (CSF-1R) on primary murine macrophages in an all-or-nothing manner. Here we show that the ability of bacterial products to down-modulate the CSF-IR rendered bone marrow-derived macrophages (BMM) unresponsive to CSF-1 as assessed by Akt and ERK 1/2 phosphorylation. Using toll-like receptor (th-)9 as a model CSF-1-repressed gene, we show that LPS induced tlr9 expression in BMM only when CSF-1 was present, suggesting that LPS relieves CSF-1-mediated inhibition to induce gene expression. Using cDNA microarrays, we identified a cluster of similarly CSF-1 repressed genes in BMM. By real time PCR we confirmed that the expression of a selection of these genes, including integral membrane protein 2B (itm2b), receptor activity-modifying protein 2 (ramp2) and macrophage-specific gene 1 (mpg-1), were repressed by CSF-1 and were induced by LPS only in the presence of CSF-1. This pattern of gene regulation was also apparent in thioglycollate-elicited peritoneal macrophages (TEPM). LPS also counteracted CSF-1 action to induce mRNA expression of a number of transcription factors including interferon consensus sequence binding protein 1 (Icsbp1), suggesting that this mechanism leads to transcriptional reprogramming in macrophages. Since the majority of in vitro studies on macrophage biology do not include CSF-1, these genes represent a set of previously uncharacterised LPS-inducible genes. This study identifies a new mechanism of macrophage activation, in which LPS (and other toll-like receptor agonists) regulate gene expression by switching off the CSF-1R signal. This finding also provides a biological relevance to the well-documented ability of macrophage activators to down-modulate surface expression of the CSF-1R. (C) 2005 Elsevier GmbH. All rights reserved.
Keyword Csf-1
Gene Regulation
Colony-stimulating Factor
Toll-like Receptors
Peritoneal-exudate Macrophages
Marrow-derived Macrophages
Mouse Macrophages
Bacterial Lipopolysaccharide
Q-Index Code C1

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Created: Wed, 15 Aug 2007, 05:55:15 EST