Inhibitory effect of anethole on T-lymphocyte proliferation and interleukin-2 production through down-regulation of the NF-AT and AP-1.
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.
Department of Biochemistry, College of Medicine, Inje University, 633-165 Gaegum-dong, Busanjin-gu, Busan 614-735, Republic of Korea. ssyea@inje.ac.kr
Sung Su
SS
Yea
Haeng-Soon
HS
Jeong
Chun Yeon
CY
Choi
Kyung-Ran
KR
Park
Sangtaek
S
Oh
Jae-Gook
JG
Shin
Chul-Ho
CH
Yun
D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050816:Octamer Transcription Factor-6 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D007376:Interleukin-2; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D003208:Concanavalin A; D050816:Octamer Transcription Factor-6; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate; C006578:anethole