title: The hydroxyflavone, fisetin, suppresses mast cell activation induced by interaction with activated T cell membranes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: National Food Research Institute, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nagai
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: I
authors.initials: I
authors.lastname: Mikami
authors.forename: T
authors.initials: T
authors.lastname: Fukusima
authors.forename: H
authors.initials: H
authors.lastname: Oike
authors.forename: M
authors.initials: M
authors.lastname: Kobori
mesh_terms: D019013:CD40 Antigens / Q000096:biosynthesis; D015550:Cell Degranulation; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D053804:Granzymes / Q000096:biosynthesis; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D054353:Perforin / Q000096:biosynthesis; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D019013:CD40 Antigens; D005419:Flavonoids; D044948:Flavonols; D016328:NF-kappa B; D054353:Perforin; D018799:Intercellular Adhesion Molecule-1; D051550:I-kappa B Kinase; D020928:Mitogen-Activated Protein Kinases; D053804:Granzymes; C017875:fisetin
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