Suppression of interleukin-2 gene expression by isoeugenol is mediated through down-regulation of NF-AT and NF-kappaB.
Isoeugenol is a naturally occurring methoxyphenol found in a variety of foods and essential oils. We investigated the effect of isoeugenol on T-cell function and the regulatory mechanism underlying its effect. Isoeugenol and its structural analog eugenol suppressed the lymphoproliferative response to concanavalin A stimulation in B6C3F1 mouse splenocyte cultures. Isoeugenol inhibited phorbol 12-myristate 13-acetate (PMA) plus ionomycin (Io)-induced IL-2 mRNA expression and protein secretion in B6C3F1 mouse splenocytes, and in EL4.IL-2 mouse T-cells, as determined by real-time RT-PCR and ELISA, respectively. To further characterize the inhibitory mechanism of isoeugenol at the transcriptional level, we examined the DNA binding activity of the transcription factors for IL-2 using an electrophoretic mobility shift assay. Isoeugenol decreased the binding activity of NF-AT and NF-kappaB in PMA/Io-stimulated EL4.IL-2 cells, but no significant effect was observed for AP-1 or Oct binding activity. Western blot analysis showed that isoeugenol also decreased the nuclear translocation of cytoplasmic NF-AT and NF-kappaB. These results suggest that isoeugenol suppresses IL-2 production through a decrease of IL-2 mRNA expression and that the inhibition is mediated, at least in part, through the down-regulation of NF-AT and NF-kappaB.
Park
Kyung-Ran
KR
Department of Biochemistry, College of Medicine, Inje University, 633-165 Gaegum-dong, Busanjin-gu, Busan 614-735, Republic of Korea.
Lee
Jung-Hee
JH
Choi
ChunYeon
C
Liu
Kwang-Hyeon
KH
Seog
Dae-Hyun
DH
Kim
Yong-Ho
YH
Kim
Dong-Eun
DE
Yun
Chul-Ho
CH
Yea
Sung Su
SS
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000502:physiology*; D005054:Eugenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D007376:Interleukin-2; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D005054:Eugenol; C036643:isoeugenol