Identification of Biological Markers of Liver X Receptor (LXR) Activation at the Cell Surface of Human Monocytes

Rébé, Cédric; Filomenko, Rodolphe; Raveneau, Magalie; Chevriaux, Angélique; Ishibashi, Minako; Lagrost, Laurent; Junien, Jean Louis; Gambert, Philippe; Masson, David
November 2012
PLoS ONE;Nov2012, Vol. 7 Issue 11, Special section p1
Academic Journal
Background: Liver X receptor (LXR) a and LXR b (NR1H3 and NR1H2) are oxysterol-activated nuclear receptors involved in the control of major metabolic pathways such as cholesterol homeostasis, lipogenesis, inflammation and innate immunity. Synthetic LXR agonists are currently under development and could find applications in various fields such as cardiovascular diseases, cancer, diabetes and neurodegenerative diseases. The clinical development of LXR agonists requires the identification of biological markers for pharmacodynamic studies. In this context, monocytes represent an attractive target to monitor LXR activation. They are easily accessible cells present in peripheral blood; they express LXR a and b and respond to LXR agonist stimulation in vitro. The aim of our study was to identify cell surface markers of LXR agonists on monocytes. For this, we focused on clusters of differentiation (CD) markers because they are well characterized and accessible cell surface molecules allowing easy immuno-phenotyping. Methodology/Principal Findings:By using microarray analysis of monocytes treated or not with an LXR agonist in vitro, we selected three CD, i.e. CD82, CD226, CD244 for further analysis by real time PCR and flow cytometry. The three CD were upregulated by LXR agonist treatment in vitro in a time- and dose- dependent manner and this induction was LXR specific as assessed by a SiRNA or LXR antagonist strategy. By using flow cytometry, we could demonstrate that the expression of these molecules at the cell surface of monocytes was significantly increased after LXR agonist treatment. Conclusions/Significance:We have identified three new cell surface markers that could be useful to monitor LXR activation. Future studies will be required to confirm the biological and diagnostic significance of the markers.


Related Articles

  • Quantification of VEGFRs, NRP1, and PDGFRs on Endothelial Cells and Fibroblasts Reveals Serum, Intra-Family Ligand, and Cross-Family Ligand Regulation. Chen, Si; Guo, Xinyi; Imarenezor, Osazomon; Imoukhuede, P. // Cellular & Molecular Bioengineering;Sep2015, Vol. 8 Issue 3, p383 

    Computational modeling of angiogenesis is limited by a lack of experimental data on angiogenic receptor levels. Recent receptor profiling quantified vascular endothelial growth factor receptors (VEGFRs); however data on other angiogenic receptors, such as platelet derived growth factor receptors...

  • The power of VEGF (vascular endothelial growth factor) family molecules. Thomas, Jean-Leon; Eichmann, Anne // Cellular & Molecular Life Sciences;May2013, Vol. 70 Issue 10, p1673 

    Vascular endothelial growth factors (VEGFs) and their high-affinity tyrosine kinase VEGF receptors (VEGFRs) are key regulators of both angiogenesis and neurogenesis. The current issue of CMLS discusses recent literature and work implementing these signals in nervous system development,...

  • Galectin-1 induces vascular permeability through the neuropilin-1/vascular endothelial growth factor receptor-1 complex. Wu, Ming-Heng; Ying, Nien-Wen; Hong, Tse-Ming; Chiang, Wei-Fan; Lin, Yueh-Te; Chen, Yuh-Ling // Angiogenesis;Oct2014, Vol. 17 Issue 4, p839 

    Galectin-1 (Gal-1) is a β-galactoside-binding lectin that regulates endothelial cell migration, proliferation, and adhesion. However, the effect of Gal-1 on vascular permeability and the underlying mechanisms are unclear. We found that high Gal-1 expression was associated with elevated tumor...

  • Endosome-to-Plasma Membrane Recycling of VEGFR2 Receptor Tyrosine Kinase Regulates Endothelial Function and Blood Vessel Formation. Jopling, Helen M.; Odell, Adam F.; Pellet-Many, Caroline; Latham, Antony M.; Frankel, Paul; Sivaprasadarao, Asipu; Walker, John H.; Zachary, Ian C.; Ponnambalam, Sreenivasan // Cells (2073-4409);Jun2014, Vol. 3 Issue 2, p363 

    Rab GTPases are implicated in endosome-to-plasma membrane recycling, but how such membrane traffic regulators control vascular endothelial growth factor receptor 2 (VEGFR2/KDR) dynamics and function are not well understood. Here, we evaluated two different recycling Rab GTPases, Rab4a and...

  • High glucose induces human endothelial dysfunction through an Axl-dependent mechanism. Chien-Hsing Lee; Yi-Shing Shieh; Fone-Ching Hsiao; Feng-Chih Kuo; Chih-Yuan Lin; Chang-Hsun Hsieh; Yi-Jen Hung // Cardiovascular Diabetology;2014, Vol. 13 Issue 1, p1 

    Background The receptor tyrosine kinase Axl and its ligand growth arrest-specific protein 6 (Gas6) are involved in the diabetic vascular disease. The aim of this study was to explore the role of Gas6/Axl system in high glucose (HG)-induced endothelial dysfunction. Methods We investigated the...

  • Involvement of αβ integrin in gremlin-induced angiogenesis. Ravelli, Cosetta; Mitola, Stefania; Corsini, Michela; Presta, Marco // Angiogenesis;Jan2013, Vol. 16 Issue 1, p235 

    αβ integrin modulates pro-angiogenic endothelial cell (EC) responses following vascular endothelial growth factor receptor-2 (VEGFR2) engagement. The bone morphogenic protein antagonist gremlin is a novel non-canonical VEGFR2 ligand that promotes the acquisition of a pro-angiogenic...

  • ADAMTS13 and its variants promote angiogenesis via upregulation of VEGF and VEGFR2. Lee, Manfai; Keener, Justin; Xiao, Juan; Long Zheng, X.; Rodgers, George // Cellular & Molecular Life Sciences;Jan2015, Vol. 72 Issue 2, p349 

    Severe plasma ADAMTS13 deficiency results in the clinical disorder thrombotic thrombocytopenic purpura. However, other potential pathophysiological roles of ADAMTS13 in endothelial cell biology remain unexplored. The goals of this study were to understand the angiogenic pathways ADAMTS13...

  • Ferula gummosa Boiss flower and leaf extracts inhibit angiogenesis in vitro. Mirzaaghaei, S.; Akrami, H.; Asadi, M. H.; Mahdiuni, H. // Indian Journal of Cancer;Oct-Dec2014, Vol. 51 Issue 4, p615 

    Background: Angiogenesis is a vital process in development as well as in tumor metastasis. Therefore, inhibition of tumor angiogenesis may be an approach for cancer therapy. In this study, we evaluated the effect of Ferula gummosa Boiss flower and leaf extracts on...

  • VEGFR1 and VEGFR2 Involvement in Extracellular Galectin-1- and Galectin-3-Induced Angiogenesis. D'Haene, Nicky; Sauvage, Sébastien; Maris, Calliope; Adanja, Ivan; Le Mercier, Marie; Decaestecker, Christine; Baum, Linda; Salmon, Isabelle // PLoS ONE;Jun2013, Vol. 8 Issue 6, p1 

    Aim: Accumulating evidence suggests that extracellular galectin-1 and galectin-3 promote angiogenesis. Increased expression of galectin-1 and/or galectin-3 has been reported to be associated with tumour progression. Thus, it is critical to identify their influence on angiogenesis. Methods: We...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics