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In this report, we show that induction of macrophage proliferation by the growth factor M-CSF is negatively modulated by agonists that activate the nuclear receptor liver X receptor (LXR), both in vitro and in vivo. Both isoforms LXR \u03b1 and \u03b2 are involved in the antiproliferative actions of LXR ligands in macrophages. In contrast, M-CSF does not exert negative effects on LXR-mediated gene expression. Treatment with LXR agonists results in the accumulation of macrophages in the G0\/G1 phase of the cell cycle without affecting ERK-1\/2 phosphorylation. The use of small interfering RNA or genetically modified mice revealed that, in contrast to other cellular models, functional expression of either the cyclin-dependent kinase inhibitor p27KIP1 or the cholesterol transporters ATP-binding cassette A1 or ATP-binding cassette G1 was not required for the antiproliferative effects of LXR agonists in macrophages. Western blot analysis revealed that protein expression of key molecules that regulate progression through the cell cycle, such as cyclins D1 and B1 and cyclin-dependent kinases 2 and 4, was downregulated upon LXR activation. These observations suggest a role for LXR agonists in limiting macrophage proliferative responses associated to pathogenic disorders.<\/jats:p>","DOI":"10.4049\/jimmunol.1000585","type":"journal-article","created":{"date-parts":[[2011,3,14]],"date-time":"2011-03-14T04:01:37Z","timestamp":1300075297000},"page":"4656-4667","source":"Crossref","is-referenced-by-count":31,"title":["Liver X Receptors Inhibit Macrophage Proliferation through Downregulation of Cyclins D1 and B1 and Cyclin-Dependent Kinases 2 and 4"],"prefix":"10.1093","volume":"186","author":[{"given":"M\u00f3nica","family":"Pascual-Garc\u00eda","sequence":"first","affiliation":[{"name":"Nuclear Receptor Group, Department of Physiology, School of Biology, University of Barcelona , 08028 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M","family":"Carb\u00f3","sequence":"additional","affiliation":[{"name":"Nuclear Receptor Group, Department of Physiology, School of Biology, University of Barcelona , 08028 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Le\u00f3n","sequence":"additional","affiliation":[{"name":"Nuclear Receptor Group, Department of Physiology, School of Biology, University of Barcelona , 08028 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Matalonga","sequence":"additional","affiliation":[{"name":"Nuclear Receptor Group, Department of Physiology, School of Biology, University of Barcelona , 08028 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruud","family":"Out","sequence":"additional","affiliation":[{"name":"Division of Biopharmaceutics, Leiden\/Amsterdam Center for Drug Research, Leiden University , 2300 RA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Van Berkel","sequence":"additional","affiliation":[{"name":"Division of Biopharmaceutics, Leiden\/Amsterdam Center for Drug Research, Leiden University , 2300 RA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Rosa","family":"Sarrias","sequence":"additional","affiliation":[{"name":"Health Sciences Research Institute, \u201cGermans Trias i Pujol\u201d Foundation , 08916 Badalona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Lozano","sequence":"additional","affiliation":[{"name":"Servei d'Immunologia, Hospital Cl\u00ednic de Barcelona, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer , 08036 Barcelona ,","place":["Spain"]},{"name":"Department of Cellular Biology, Immunology and Neurosciences, School of Medicine, University of Barcelona , 08036 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Celada","sequence":"additional","affiliation":[{"name":"Macrophage Biology Group, Institute for Research in Biomedicine , 08028 Barcelona ,","place":["Spain"]},{"name":"Department of Physiology, School of Biology, University of Barcelona , 08028 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabel F","family":"Valledor","sequence":"additional","affiliation":[{"name":"Nuclear Receptor Group, Department of Physiology, School of Biology, University of Barcelona , 08028 Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,4,15]]},"reference":[{"key":"2025032411202973600_r1","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1002\/eji.200737638","article-title":"The macrophage: past, present and future","volume":"37","author":"Gordon","year":"2007","journal-title":"Eur. 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