IL-4 and interferon gamma regulate expression of inducible nitric oxide synthase in chronic lymphocytic leukemia cells
| Autor: | D L Wilson, Youwei Chen, Bethany E. Beasley, R Silber, Charles W. O’Loughlin, Mary A. Misukonis, David J. Adams, JB Weinberg, Marc C. Levesque |
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| Rok vydání: | 2003 |
| Předmět: |
Cancer Research
Nitric Oxide Synthase Type III Chronic lymphocytic leukemia medicine.medical_treatment Nitric Oxide Synthase Type II Biology Gene Expression Regulation Enzymologic Nitric oxide chemistry.chemical_compound Tumor Cells Cultured medicine Humans Interferon gamma RNA Messenger Interleukin 4 B-Lymphocytes Reverse Transcriptase Polymerase Chain Reaction Hematology medicine.disease Leukemia Lymphocytic Chronic B-Cell Gene Expression Regulation Neoplastic Nitric oxide synthase Haematopoiesis Leukemia Cytokine Oncology chemistry Leukemia Myeloid Immunology Cancer research biology.protein Interleukin-4 Nitric Oxide Synthase medicine.drug |
| Zdroj: | Leukemia. 17:442-450 |
| ISSN: | 1476-5551 0887-6924 |
| DOI: | 10.1038/sj.leu.2402783 |
| Popis: | Chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of long-lived non-dividing CD5(+) B cells. Nitric oxide (NO) is an important regulator of apoptosis, and the viability of cultured B-CLL cells may be dependent on the autocrine production of nitric oxide by inducible nitric oxide synthase (NOS2). We performed this study to determine whether cytokine factors that prevent spontaneous in vitroapoptosis of B-CLL cells induce B-CLL cell NOS2 enzyme activity. B-CLL cells expressed NOS enzyme activity and NOS2 protein and mRNA. IL-4 and IFN-gamma increased B-CLL cell NOS2 enzyme activity and protein expression during in vitro culture. IFN-gamma, but not IL-4, increased NOS2 mRNA expression in cultured B-CLL cells suggesting that IL-4-mediated changes of NOS2 protein expression occurred at the post-transcriptional level. We were unable to detect increased concentrations of nitrite or nitrate (NO(x)) as surrogate markers of NO production in B-CLL cell cultures treated with IL-4 or IFN-gamma. IL-4 and IFN-gamma diminished NOS inhibitor-induced B-CLL cell death. In summary, we found that B-CLL cells expressed NOS2 and that IL-4 and IFN-gamma increased B-CLL NOS2 expression. Cytokine-mediated expression of NOS2 by B-CLL cells may promote their survival, and therapeutic strategies that target NOS2 or quench NO may be beneficial in patients with B-CLL. |
| Databáze: | OpenAIRE |
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