2026-04-17T14:28:28Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2226132026-02-05T21:54:30Zcom_2072_1057col_2072_478780col_2072_478917

00925njm 22002777a 4500 dc Pascual García, Mónica author Carbó, José M. author León Moreno, Theresa Elizabeth author Matalonga, Jonathan author Out, Ruud author Van Berkel, Theo author Sarrias Fornés, Maria Rosa author Lozano, Francisco author Celada Cotarelo, Antonio author Valledor Fernández, Annabel author 2025-07-28T09:48:37Z 2011-04-15 2025-07-28T09:48:37Z info:eu-repo/semantics/embargoEnd/2099-01-01T09:48:37Z Macrophages serve essential functions as regulators of immunity and homeostasis, and their proliferation contributes to pathogenesis of certain disorders. 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 α and β 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. Genètica Immunitat Homeòstasi Macròfags Genetics Immunity Homeostasis Macrophages Liver X Receptors Inhibit Macrophage Proliferation through Downregulation of Cyclins D1 and B1 and Cyclin-Dependent Kinases 2 and 4