Liver X receptors interfere with cytokine-induced proliferation and cell survival in normal and leukemic lymphocytes
| Autor: | Karl M. Stuhlmeier, René Geyeregger, Medhat Shehata, Edit Porpaczy, Gerhard J. Zlabinger, Ulrich Jäger, Thomas M. Stulnig, Maximilian Zeyda, Florian W. Kiefer |
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| Rok vydání: | 2009 |
| Předmět: |
0303 health sciences
biology medicine.medical_treatment Immunology Retinoblastoma protein Cell Biology Dendritic cell Cell cycle medicine.disease 3. Good health Cell biology 03 medical and health sciences Leukemia 0302 clinical medicine Cytokine Nuclear receptor medicine biology.protein Immunology and Allergy lipids (amino acids peptides and proteins) Viability assay Liver X receptor 030304 developmental biology 030215 immunology |
| Zdroj: | Journal of Leukocyte Biology. 86:1039-1048 |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | A novel role for Liver X receptors in lymphocytic cells is described with potential application in immunosuppression and anti-leukemia therapy. 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. |
| Databáze: | OpenAIRE |
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