6-Methoxyflavone Inhibits NFAT Translocation into the Nucleus and Suppresses T Cell Activation
SCIE
SCOPUS
- Title
- 6-Methoxyflavone Inhibits NFAT Translocation into the Nucleus and Suppresses T Cell Activation
- Authors
- Jae-Seon So; Gi-Cheon Kim; MinKyung Song; Choong-Gu Lee; Eunbee Park; Ho Jin Kim; Young Sup Kim; Chang-Duk Jun; Im, SH
- Date Issued
- 2014-09
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Abstract
- NFAT plays a crucial role in the immune system by regulating the transcription of inducible genes during immune responses. In T cells, NFAT proteins govern various cellular events related to T cell development, activation, tolerance induction, and differentiation. We previously reported the NFAT1-dependent enhancer activity of conserved noncoding sequence (CNS)-9, a distal cis-acting element, in the regulation of IL-10 transcription in T cells. In this study, we developed a T cell-based reporter system to identify compounds that modulate the regulatory activity of CNS-9. Among the identified candidates, 6-methoxyflavone (6-MF) significantly inhibited the enhancer activity of CNS-9, thereby reducing IL-10 expression in T cells without affecting cell viability. 6-MF also downregulated the transcription of NFAT1 target genes such as IL-4, IL-13, and IFN-gamma. Treatment of 6-MF inhibited the translocation of NFAT1 into the nucleus, which consequently interrupted NFAT1 binding to the target loci, without affecting the expression or dephosphorylation of NFAT1. Treatment of 6-MF to CD4(+) T cells or B cells isolated from mice with atopic dermatitis significantly reduced disease-associated cytokine production, as well as the levels of IgE. In addition, oral administration of 6-MF to atopic dermatitis mice ameliorated disease symptoms by reducing serum IgE levels and infiltrating lymphocytes. Conclusively, our results suggest that 6-MF can be a potential candidate for the development of an effective immunomodulator via the suppression of NFAT-mediated T cell activation.
- Keywords
- TRANSCRIPTION FACTOR NFAT; CYCLOSPORINE-A; MOLECULAR-MECHANISMS; CYTOKINE PRODUCTION; ATOPIC-DERMATITIS; GENE-EXPRESSION; IN-VIVO; CALCINEURIN; FLAVONOIDS; LYMPHOCYTES
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/13736
- DOI
- 10.4049/JIMMUNOL.1400285
- ISSN
- 0022-1767
- Article Type
- Article
- Citation
- JOURNAL OF IMMUNOLOGY, vol. 193, no. 6, page. 2772 - 2783, 2014-09
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