The hydroxyflavone, fisetin, suppresses mast cell activation induced by interaction with activated T cell membranes

Br J Pharmacol. 2009 Oct;158(3):907-19. doi: 10.1111/j.1476-5381.2009.00365.x. Epub 2009 Aug 20.

Abstract

Background and purpose: Cell-to-cell interactions between mast cells and activated T cells are increasingly recognized as a possible mechanism in the aetiology of allergic or non-allergic inflammatory disorders. To determine the anti-allergic effect of fisetin, we examined the ability of fisetin to suppress activation of the human mast cell line, HMC-1, induced by activated Jurkat T cell membranes.

Experimental approach: HMC-1 cells were incubated with or without fisetin for 15 min and then co-cultured with Jurkat T cell membranes activated by phorbol-12-myristate 13-acetate for 16 h. We determined gene expression in activated HMC-1 cells by DNA microarray and quantitative reverse transcription (RT)-PCR analysis. We also examined activation of the transcription factor NF-kappaB and MAP kinases (MAPKs) in activated HMC-1 cells.

Key results: Fisetin suppresses cell spreading and gene expression in HMC-1 cells stimulated by activated T cell membranes. Additionally, we show that these stimulated HMC-1 cells expressed granzyme B. The stimulatory interaction also induced activation of NF-kappaB and MAPKs; these activations were suppressed by fisetin. Fisetin also reduced the amount of cell surface antigen CD40 and intercellular adhesion molecule-1 (ICAM-1) on activated HMC-1 cells.

Conclusions and implications: Fisetin suppressed activation of HMC-1 cells by activated T cell membranes by interfering with cell-to-cell interaction and inhibiting the activity of NF-kappaB and MAPKs and thereby suppressing gene expression. Fisetin may protect against the progression of inflammatory diseases by limiting interactions between mast cells and activated T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD40 Antigens / biosynthesis
  • Cell Degranulation
  • Cell Line
  • Cell Line, Tumor
  • Cell Membrane / physiology*
  • Flavonoids / pharmacology*
  • Granzymes / biosynthesis
  • Humans
  • I-kappa B Kinase / metabolism
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Mast Cells / cytology
  • Mast Cells / drug effects*
  • Mast Cells / physiology
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Perforin / biosynthesis
  • Phosphorylation
  • T-Lymphocytes / physiology*
  • T-Lymphocytes / ultrastructure

Substances

  • CD40 Antigens
  • Flavonoids
  • NF-kappa B
  • Perforin
  • Intercellular Adhesion Molecule-1
  • I-kappa B Kinase
  • Mitogen-Activated Protein Kinases
  • Granzymes
  • fisetin