Abstract
Anethole is a naturally occurring alkenylbenzene found in a variety of foods and essential oils. In the present study, we investigated the effect of anethole on T-cell function and the regulatory mechanism of its effect. Direct addition of anethole to B6C3F1 mouse splenocyte cultures produced a concentration-dependent inhibition of the lymphoproliferative response to concanavalin A stimulation. Anethole inhibited phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io)-induced interleukin-2 (IL-2) mRNA expression and protein secretion in EL4 mouse T-cells as determined by quantitative/competitive RT-PCR and ELISA, respectively. To further characterize the mechanism for the transcriptional regulation of IL-2, an electrophoretic mobility shift assay was performed to evaluate the binding activity of the nuclear factor of activated T-cells (NF-AT), activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB), and octamer binding protein (Oct) in PMA/Io-stimulated EL4 cells. Anethole decreased the NF-AT and AP-1 binding activity, but no significant effect was observed on NF-kappaB or Oct binding activity. These results suggest that anethole suppress T-cell proliferation and IL-2 production and that the inhibition is mediated, at least in part, through the down-regulation of NF-AT and AP-1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allylbenzene Derivatives
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Animals
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Anisoles / chemistry
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Anisoles / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects*
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Cells, Cultured
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Concanavalin A / pharmacology
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Dose-Response Relationship, Drug
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Down-Regulation / drug effects
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Enzyme-Linked Immunosorbent Assay
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Female
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Interleukin-2 / genetics
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Interleukin-2 / metabolism*
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Ionomycin / pharmacology
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Lipopolysaccharides / pharmacology
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Mice
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Mice, Inbred Strains
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NF-kappa B / drug effects
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NF-kappa B / genetics
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NF-kappa B / metabolism
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NFATC Transcription Factors / genetics
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NFATC Transcription Factors / metabolism*
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Octamer Transcription Factor-6 / genetics
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Octamer Transcription Factor-6 / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Spleen / cytology
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Spleen / drug effects
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Spleen / metabolism
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects*
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T-Lymphocytes / metabolism
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Tetradecanoylphorbol Acetate / pharmacology
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism*
Substances
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Allylbenzene Derivatives
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Anisoles
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Interleukin-2
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Lipopolysaccharides
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NF-kappa B
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NFATC Transcription Factors
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RNA, Messenger
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Transcription Factor AP-1
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Concanavalin A
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Octamer Transcription Factor-6
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Ionomycin
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Tetradecanoylphorbol Acetate
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anethole