Accuri C6 Flow Cytometer System
Originally published online as doi:10.1189/jlb.1008663 on August 11, 2009

Published online before print August 11, 2009
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(Journal of Leukocyte Biology. 2009;86:1039-1048.)
© 2009 Society for Leukocyte Biology

Liver X receptors interfere with cytokine-induced proliferation and cell survival in normal and leukemic lymphocytes

René Geyeregger*,1, Medhat Shehata{dagger},{ddagger},1, Maximilian Zeyda*, Florian W. Kiefer*, Karl M. Stuhlmeier§, Edit Porpaczy{dagger}, Gerhard J. Zlabinger||, Ulrich Jäger{dagger} and Thomas M. Stulnig*,2

Departments of
* Internal Medicine III, Clinical Divisions of Endocrinology and Metabolism, and
{dagger} Internal Medicine I, Clinical Divisions of Hematology and Hemostaseology,
|| Institute of Immunology, and
{ddagger} Karl Landsteiner Institute for Cytokine and Tumor Microenvironment, Medical University of Vienna, Vienna, Austria; and
§ Ludwig Boltzmann Institute for Rheumatology, Vienna, Austria

2. Correspondence: Clinical Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. E-mail: thomas.stulnig{at}meduniwien.ac.at

ABSTRACT

Liver X receptors (LXRs) are nuclear receptors regulating lipid and cholesterol metabolism. Recent data indicate an additional role of LXR in immunity by controlling dendritic cell and T-cell function and in breast and prostate cancer cells. Here, we show that LXR activation interferes with IL-2 and IL-7-induced proliferation and cell cycle progression of human T-cell blasts mainly through inhibited phosphorylation of the retinoblastoma protein and decreased expression of the cell cycle protein cyclin B. Comparable results were obtained with IL-2-dependent chronic lymphoblastic leukemia (CLL) T cells. Furthermore, we show for B-CLL cells that LXR are functionally active and inhibit expression of survival genes bcl-2 and MMP-9, and significantly reduce cell viability, suggesting an interference of LXR with cytokine-dependent CLL cell survival. In conclusion, our data reveal LXR as a potent modulator of cytokine-dependent proliferation and survival of normal and malignant T and B lymphocytes. This novel LXR action could find clinical application in immunosuppressive and antileukemic therapies.

Key Words: cell cycle • T lymphoblasts • T cell and B cell chronic lymphoblastic leukemia


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Editorial: Liver X receptor {alpha} (LXR{alpha}) as a therapeutic target in chronic lymphocytic leukemia (CLL)
Kent W. Christopherson, II and Alan Landay
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K. W. Christopherson II and A. Landay
Editorial: Liver X receptor {alpha} (LXR{alpha}) as a therapeutic target in chronic lymphocytic leukemia (CLL)
J. Leukoc. Biol., November 1, 2009; 86(5): 1019 - 1021.
[Full Text] [PDF]