Piceatannol is an effective inhibitor of IgE-mediated secretion from human basophils but is neither selective for this receptor nor acts on syk kinase at concentrations where mediator release inhibition occurs

K. Miura, S. Lavens-Phillips, D. W. MacGlashan

Research output: Contribution to journalArticle

Abstract

Background: Syk kinase is probably an early necessary tyrosine kinase involved in IgE-mediated secretion from human basophils. Causal testing of the role ofsyk kinase in the secretion requires a selective pharmacological agent. Piceatannol has previously been used to demonstrate the causal role of syk in secretion but its selectively has recently come into question. Objective: To determine whether piceatannol inhibits IgE-mediated signalling events in a manner consistent with its putative inhibitory effects on syk kinase and at concentrations relevant to its inhibition of mediator release. Methods: Human basophils were examined for the effects of piceatannol on mediator release or various signalling steps. Results: We show that while piceatannol has an IC50 for inhibition of IgE-mediated histamine release of 3-5 μM, these same concentrations inhibit secretion of phorbol 12-myristate 13-acetate (PMA)-induced histamine release (as previously shown) and leukotriene C (LTC)4 release induced by fMLP. Concentrations of piceatannol up to 100 μM also did not inhibit IgE-mediated phosphorylation of shc, a immediate downstream target of syk kinase. Similar concentrations also did not inhibit IgE-mediated cytosolic calcium elevations, another downstream signal thought to be dependent on syk kinase. In contrast, piceatannol did modify the cytosolic calcium response that follows stimulation with formyl methionyl-leucyl-phenylalanine (fMLP). Conclusion: Taken together with published studies using other cell types, we conclude that piceatannol does not inhibit secretion from human basophils by inhibiting the activity of syk kinase.

Original languageEnglish (US)
Pages (from-to)1732-1739
Number of pages8
JournalClinical and Experimental Allergy
Volume31
Issue number11
DOIs
StatePublished - Dec 1 2001

Keywords

  • Anti-IgE
  • Calcium
  • Formyl-met-leu-phe
  • Histamine release
  • Human basophils
  • LTC4 release
  • Phorbol ester
  • Piceatannol
  • Shc
  • Syk kinase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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