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

David P. Sester, Angela Trieu, Kristian Brion, Kate Schroder, Timothy Ravasi, Jodie A. Robinson, Rebecca C. McDonald, Vera Ripoll, Christine A. Wells, Harukazu Suzuki, Yoshihide Hayashizaki, Katryn J. Stacey, David A. Hume, Matthew J. Sweet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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-1R rendered bone marrow-derived macrophages (BMM) unresponsive to CSF-1 as assessed by Akt and ERK1/2 phosphorylation. Using toll-like receptor (tlr)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 micro-arrays, 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.

Original languageEnglish (US)
Pages (from-to)97-107
Number of pages11
Issue number2-4
StatePublished - Aug 19 2005
Externally publishedYes

Bibliographical note

Funding Information:
The authors are grateful for funding from the National Health and Medical Research Council of Australia (ID 301210, 301211) and from the Coley Pharmaceutical Group (Iowa City, AI), and for the facilities provided by the Special Research Centre for Functional and Applied Genomics and the Micro-array Facility at the University of Queensland.


  • CSF-1
  • Gene regulation
  • Inflammation
  • Lipopolysaccharide
  • Micro-array
  • Monocytes/macrophages
  • TLR9

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology


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