Curcumin blocks interleukin (IL)-2 signaling in T-lymphocytes by inhibiting IL-2 synthesis, CD25 expression, and IL-2 receptor signaling
| Autor: | Nicholas A. Forward, David W. Hoskin, David M. Conrad, Carolyn D. Doucette, Melanie R. Power Coombs, Suzanne J. Furlong, Tong-Jun Lin |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Curcumin
Cell Survival T-Lymphocytes CD3 Biophysics Biology Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine STAT5 Transcription Factor Animals Curcuminoid Receptor Molecular Biology Transcription factor Cell Proliferation 030304 developmental biology 0303 health sciences DNA synthesis Interleukin-2 Receptor alpha Subunit Janus Kinase 3 JAK-STAT signaling pathway Receptors Interleukin-2 Cell Biology Molecular biology 3. Good health Mice Inbred C57BL chemistry 030220 oncology & carcinogenesis biology.protein Interleukin-2 Phosphorylation Female Immunosuppressive Agents Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 407:801-806 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2011.03.103 |
| Popis: | Curcumin (diferulomethane) is the principal curcuminoid in the spice tumeric and a potent inhibitor of activation-induced T-lymphocyte proliferation; however, the molecular basis of this immunosuppressive effect has not been well studied. Here we show that micromolar concentrations of curcumin inhibited DNA synthesis by mouse CD4(+) T-lymphocytes, as well as interleukin-2 (IL-2) and CD25 (α chain of the high affinity IL-2 receptor) expression in response to antibody-mediated cross-linking of CD3 and CD28. Curcumin acted downstream of protein kinase C activation and intracellular Ca(2+) release to inhibit IκB phosphorylation, which is required for nuclear translocation of the transcription factor NFκB. In addition, IL-2-dependent DNA synthesis by mouse CTLL-2 cells, but not constitutive CD25 expression, was impaired in the presence of curcumin, which demonstrated an inhibitory effect on IL-2 receptor (IL-2R) signaling. IL-2-induced phosphorylation of STAT5A and JAK3, but not JAK1, was diminished in the presence of curcumin, indicating inhibition of critical proximal events in IL-2R signaling. In line with the inhibitory action of curcumin on IL-2R signaling, pretreatment of CD4(+)CD25(+) regulatory T-cells with curcumin downregulated suppressor function, as well as forkhead box p3 (Foxp3) expression. We conclude that curcumin inhibits IL-2 signaling by reducing available IL-2 and high affinity IL-2R, as well as interfering with IL-2R signaling. |
| Databáze: | OpenAIRE |
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