Heptamethoxyflavone Reduces Phosphodiesterase Activity and T-Cell Growth in vitro

Int Arch Allergy Immunol. 2017;174(3-4):113-120. doi: 10.1159/000481094. Epub 2017 Nov 8.

Abstract

In a previous study, we reported that interleukin-4 production was reduced in spleen cells of mice administered 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), which is a polymethoxyflavone found at high concentrations in the peel of various citrus fruits. In this study, we investigated the function of HMF on the growth of T cells cultured from the spleens of mice. HMF decreased the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) by anti-CD3/CD28 antibody-stimulated mouse spleen cells. HMF inhibited the activities of phosphodiesterase (PDE) enzymes prepared from bovine brain and human PDE4B and PDE3B enzymes. The cyclic AMP (cAMP) content in anti-CD3/CD28 antibody-stimulated spleen cells increased after HMF treatment in vitro. These results suggest that HMF inhibits T-cell growth and affects immune function via reduced PDE activity and increased cAMP content.

Keywords: Cyclic AMP; Heptamethoxyflavone; Phosphodiesterase; Spleen cells; T cells.

MeSH terms

  • Animals
  • Cattle
  • Cell Growth Processes / drug effects*
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism
  • Female
  • Flavonoids / pharmacology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Phosphoric Diester Hydrolases / metabolism*
  • Spleen / pathology*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • Flavonoids
  • 3,3',4',5,6,7,8-heptamethoxyflavone
  • Cyclic AMP
  • Phosphoric Diester Hydrolases
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE3B protein, human
  • PDE4B protein, human