Formononetin, a phyto-oestrogen, and its metabolites up-regulate interleukin-4 production in activated T cells via increased AP-1 DNA binding activity
- Authors
- Park, J; Kim, SH; Cho, DH; Kim, TS
- Issue Date
- Sep-2005
- Publisher
- BLACKWELL PUBLISHING
- Keywords
- phyto-oestrogen; interleukin-4; allergy; AP-1; T cell
- Citation
- IMMUNOLOGY, v.116, no.1, pp 71 - 81
- Pages
- 11
- Journal Title
- IMMUNOLOGY
- Volume
- 116
- Number
- 1
- Start Page
- 71
- End Page
- 81
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/15480
- DOI
- 10.1111/j.1365-2567.2005.02199.x
- ISSN
- 0019-2805
1365-2567
- Abstract
- Phyto-oestrogens are polyphenolic non-steroidal plant compounds with oestrogen-like biological activity. Phyto-oestrogens have many biological effects including oestrogen agonist/antagonist properties. However, the effect of phyto-oestrogens on allergic responses remains unclear. In this study we investigated whether formononetin, a phyto-oestrogen, and its metabolites, daidzein and equol, affect production of interleukin-4 (IL-4), a pro-inflammatory cytokine closely associated with allergic immune response, in primary CD4(+) T cells and EL4 T lymphoma cells. Formononetin, daidzein and equol significantly enhanced IL-4 production from both CD4(+) T cells and EL4 cells in a dose-dependent manner. Formononetin, daidzein and equol also enhanced IL-4 gene promoter activity in EL4 cells transiently transfected with IL-4 gene promoter constructs, but this effect was impaired in EL4 cells transfected with an IL-4 promoter construct deleted of P4 site carrying nuclear factor of activated T cells (NF-AT) and activator protein-1 (AP-1) binding sites. In addition, formononetin, daidzein and equol increased AP-1 DNA binding activities while did not affect NF-AT DNA binding activities. The enhancing effects on IL-4 production and AP-1 DNA binding activities were abrogated by specific inhibitors for phosphatidylinositol-3-kinase (PI3K), protein kinase C (PKC) and p38 mitogen-activated protein kinase (MAPK), indicating that formononetin, daidzein and equol might enhance IL-4 production by increased activation of AP-1 through the PI3-K/PKC/p38 MAPK signalling pathway. These results suggest that phyto-oestrogens and some of their metabolites may increase allergic responses via the enhancement of IL-4 production in T cells.
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