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면역미생물공생연구단
면역 미생물 공생 연구단
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6-Methoxyflavone Inhibits NFAT Translocation into the Nucleus and Suppresses T Cell Activation

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Title
6-Methoxyflavone Inhibits NFAT Translocation into the Nucleus and Suppresses T Cell Activation
Author(s)
So, JS; Gi-Cheon Kim; Song, M; Choong-Gu Lee; Eunbee Park; Kim, HJ; Kim, YS; Jun, CD; Sin Hyeog Im
Publication Date
2014-09
Journal
JOURNAL OF IMMUNOLOGY, v.193, no.6, pp.2772 - 2783
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 cisacting 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-g. 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.
URI
https://pr.ibs.re.kr/handle/8788114/780
ISSN
0022-1767
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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