Fisetin, a flavonol, inhibits TH2-type cytokine production by activated human basophils

J Allergy Clin Immunol. 2003 Jun;111(6):1299-306. doi: 10.1067/mai.2003.1456.

Abstract

Background: Activation of mast cells and basophils through allergen stimulation releases chemical mediators and synthesizes cytokines. Among these cytokines, IL-4, IL-13, and IL-5 have major roles in allergic inflammation.

Objective: We sought to determine the potency of flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) for the inhibition of cytokine expression and synthesis by human basophils.

Methods: The inhibitory effect of flavonoids on cytokine expression by stimulated KU812 cells, a human basophilic cell line, and freshly purified peripheral blood basophils was measured by means of semiquantitative RT-PCR and ELISA assays. The effects of flavonoids on transcriptional activation of the nuclear factor of activated T cells were assessed by means of electrophoretic mobility shift assays.

Results: Fisetin suppressed the induction of IL-4, IL-13, and IL-5 mRNA expression by A23187-stimulated KU812 cells and basophils in response to cross-linkage of the IgE receptor. Fisetin reduced IL-4, IL-13, and IL-5 synthesis (inhibitory concentration of 50% [IC(50)] = 19.4, 17.7, and 17.4 micromol/L, respectively) but not IL-6 and IL-8 production by KU812 cells. In addition, fisetin inhibited IL-4 and IL-13 synthesis by anti-IgE antibody-stimulated human basophils (IC(50) = 5.1 and 6.2 micromol/L, respectively) and IL-4 synthesis by allergen-stimulated basophils from allergic patients (IC(50) = 4.8 micromol/L). Among the flavonoids examined, kaempferol and quercetin showed substantial inhibitory activities in cytokine expression but less so than those of fisetin. Fisetin inhibited nuclear localization of nuclear factor of activated T cells c2 by A23187-stimulated KU812 cells.

Conclusion: These results provide evidence of a novel activity of the flavonoid fisetin that suppresses the expression of T(H)2-type cytokines (IL-4, IL-13, and IL-5) by basophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basophils / drug effects
  • Basophils / immunology*
  • Cytokines / biosynthesis*
  • DNA-Binding Proteins / metabolism
  • Down-Regulation
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Flavonols
  • Gene Expression Regulation
  • Humans
  • Interleukin-13 / biosynthesis
  • Interleukin-13 / genetics
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Interleukin-5 / biosynthesis
  • Interleukin-5 / genetics
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • RNA, Messenger / biosynthesis
  • Th2 Cells / immunology
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured

Substances

  • Cytokines
  • DNA-Binding Proteins
  • Flavonoids
  • Flavonols
  • Interleukin-13
  • Interleukin-5
  • NFATC Transcription Factors
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Interleukin-4
  • fisetin