dc.contributor.author | P. Sester, David | |
dc.contributor.author | Trieu, Angela | |
dc.contributor.author | Brion, Kristian | |
dc.contributor.author | Schroder, Kate | |
dc.contributor.author | Ravasi, Timothy | |
dc.contributor.author | A. Robinson, Jodie | |
dc.contributor.author | McDonald, Rebecca C. | |
dc.contributor.author | Ripolla, Vera | |
dc.contributor.author | Suzuki, Harukazu | |
dc.contributor.author | Hayashizaki, Yoshihide | |
dc.contributor.author | J. Stacey, Katryn | |
dc.contributor.author | A. Hume, David | |
dc.contributor.author | Sweet, Matthew J. | |
dc.contributor.author | A. Wells, Christine | |
dc.date.accessioned | 2017-05-03T15:01:04Z | |
dc.date.available | 2017-05-03T15:01:04Z | |
dc.date.issued | 2005 | |
dc.date.modified | 2008-12-18T06:55:10Z | |
dc.identifier.issn | 01712985 | |
dc.identifier.doi | 10.1016/j.imbio.2005.05.004 | |
dc.identifier.uri | http://hdl.handle.net/10072/20921 | |
dc.description.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-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 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. | |
dc.description.peerreviewed | Yes | |
dc.description.publicationstatus | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Gustav Fischer Verlag | |
dc.publisher.place | Germany | |
dc.publisher.uri | http://www.elsevier.com/wps/find/journaldescription.cws_home/701769/description#description | |
dc.relation.ispartofstudentpublication | N | |
dc.relation.ispartofpagefrom | 97 | |
dc.relation.ispartofpageto | 107 | |
dc.relation.ispartofissue | 2-4 | |
dc.relation.ispartofjournal | Immunobiology | |
dc.relation.ispartofvolume | 210 | |
dc.rights.retention | N | |
dc.subject.fieldofresearch | Biological Sciences | |
dc.subject.fieldofresearch | Agricultural and Veterinary Sciences | |
dc.subject.fieldofresearch | Medical and Health Sciences | |
dc.subject.fieldofresearchcode | 06 | |
dc.subject.fieldofresearchcode | 07 | |
dc.subject.fieldofresearchcode | 11 | |
dc.title | LPS regulates a set of genes in primary murine macrophages by antagonising CSF-1 action | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
gro.date.issued | 2005 | |
gro.hasfulltext | No Full Text | |
gro.griffith.author | Wells, Christine | |