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Journal of the Korean Society for Applied Biological Chemistry : Volume 54, Issue 5, October 2011

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Journal of the Korean Society for Applied Biological Chemistry : Volume 53

Journal of the Korean Society for Applied Biological Chemistry : Volume 52

Down-regulation of T helper 2-associated cytokine expression and selective transcription factors by fisetin

Content Provider	Springer Nature Link
Author	Yoon, Soo Jeong Pyo, Myoung Yun Jin, Mirim
Copyright Year	2011
Abstract	Fisetin, a flavonol, has been known as an anti-allergic agent having inhibitory effects on T helper 2 cytokine gene expression in inflammatory immune cells. However, its molecular mechanisms for suppressive effects of fisetin on interleukin (IL)-4 and IL-13 in activated mast cells and basophils have been incompletely understood. In this study we found that fisetin at the concentrations having no effect on cell viability significantly inhibited the phorbol 12-myristate 13-acetate and ionomycin induced production of IL-4 and IL-13 in bone marrow-derived mast cells and RBL-2H3 basophilic cells. The levels of mRNA were dramatically decreased by fisetin, indicating the suppression might be regulated at the transcriptional levels. Transient transfection experiments using luciferase reporter plasmids expressing IL-4 or IL-13 promoter revealed that fisetin inhibited the activation of the promoters in a dose-dependent manner. Western blot analysis of the nuclear expression of various transcription factors involved in the promoter activation indicated that suppressions of c- Fos and CCAAT/enhancer-binding protein alpha were prominent together with significant downregulations of nuclear factor of activated T cell (NF-AT) and NF-κB. Furthermore, nuclear expression of GATA-1 and GATA-2, and the mRNA expression were significantly down regulated by fisetin, whereas cyclosporine A had no significant effects on GATA transcription factors. Taken together, fisetin has suppressive effects on IL-4 and IL-13 gene expressions through the regulation of selective transcription factors.
Starting Page	949
Ending Page	958
Page Count	10
File Format	PDF
ISSN	17382203
Journal	Journal of the Korean Society for Applied Biological Chemistry
Volume Number	54
Issue Number	6
e-ISSN	2234344X
Language	English
Publisher	Springer-Verlag
Publisher Date	2011-01-01
Publisher Place	New York
Access Restriction	Subscribed
Subject Keyword	transcription factors fisetin Applied Microbiology Biological Techniques basophils IL-13 interleukin (IL)-4 mast cells Bioorganic Chemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry, Genetics and Molecular Biology

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