Flavonols inhibit proinflammatory mediator release, intracellular calcium ion levels and protein kinase C theta phosphorylation in human mast cells

Authors

  • Duraisamy Kempuraj,

    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, U.S.A.
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  • Bhuvaneshwari Madhappan,

    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, U.S.A.
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  • Spyridon Christodoulou,

    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, U.S.A.
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  • William Boucher,

    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, U.S.A.
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  • Jing Cao,

    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, U.S.A.
    2. Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02111, U.S.A.
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  • Nikoletta Papadopoulou,

    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, U.S.A.
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  • Curtis L Cetrulo,

    1. Department of Obstetrics and Gynecology, Tufts-New England Medical Center, Boston, MA 02111, U.S.A.
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  • Theoharis C Theoharides

    Corresponding author
    1. Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, U.S.A.
    2. Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02111, U.S.A.
    3. Department of Internal Medicine, Tufts-New England Medical Center, Boston, MA 02111, U.S.A.
      Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, U.S.A.; E-mail: theoharis.theoharides@tufts.edu
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Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, U.S.A.; E-mail: theoharis.theoharides@tufts.edu

Abstract

  • 1Mast cells participate in allergies, and also in immunity and inflammation by secreting proinflammatory cytokines.
  • 2Flavonoids are naturally occurring polyphenolic plant compounds, one group of which – the flavonols, inhibits histamine and some cytokine release from rodent basophils and mast cells. However, the effect of flavonols on proinflammatory mediator release and their possible mechanism of action in human mast cells is not well defined.
  • 3Human umbilical cord blood-derived cultured mast cells (hCBMCs) grown in the presence of stem cell factor (SCF) and interleukin (IL)-6 were preincubated for 15 min with the flavonols quercetin, kaempferol, myricetin and morin (0.01, 0.1, 1, 10 or 100 μM), followed by activation with anti-IgE. Secretion was quantitated for IL-6, IL-8, tumor necrosis factor-alpha (TNF-α), histamine and tryptase levels.
  • 4Release of IL-6, IL-8 and TNF-α was inhibited by 82–93% at 100 μM quercetin and kaempferol, and 31–70% by myricetin and morin. Tryptase release was inhibited by 79–96% at 100 μM quercetin, kampferol and myricetin, but only 39% by morin; histamine release was inhibited 52–77% by the first three flavonols, but only 28% by morin. These flavonols suppressed intracellular calcium ion elevations in a dose–response manner, with morin being the weakest; they also inhibited phosphorylation of the calcium-insensitive protein kinase C theta (PKC θ).
  • 5Flavonol inhibition of IgE-mediated proinflammatory mediator release from hCBMCs may be due to inhibition of intracellular calcium influx and PKC θ signaling. Flavonols may therefore be suitable for the treatment of allergic and inflammatory diseases.

British Journal of Pharmacology (2005) 145, 934–944. doi:10.1038/sj.bjp.0706246

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