A mechanism of benefit of soy genistein in asthma: Inhibition of eosinophil p38-dependent leukotriene synthesis

R. Kalhan*, L. J. Smith, M. C. Nlend, A. Nair, J. L. Hixon, P. H.S. Sporn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Background: Dietary intake of the soy isoflavone genistein is associated with reduced severity of asthma, but the mechanisms responsible for this effect are unknown. Objective: To determine whether genistein blocks eosinophil leukotriene C4 (LTC4) synthesis and to evaluate the mechanism of this effect, and to assess the impact of a 4-week period of soy isoflavone dietary supplementation on indices of eosinophilic inflammation in asthma patients. Methods: Human peripheral blood eosinophils were stimulated in the absence and presence of genistein, and LTC4 synthesis was measured. 5-lipoxygenase (5-LO) nuclear membrane translocation was assessed by confocal immunofluorescence microscopy. Mitogen-activated protein (MAP) kinase activation was determined by immunoblot. Human subjects with mild-to-moderate persistent asthma and minimal or no soy intake were given a soy isoflavone supplement (100 mg/day) for 4 weeks. The fraction of exhaled nitric oxide (FENO) and ex vivo eosinophil LTC4 production were assessed before and after the soy isoflavone treatment period. Results: Genistein inhibited eosinophil LTC4 synthesis (IC50 80 nm), blocked phosphorylation of p38 MAP kinase and its downstream target MAPKAP-2, and reduced translocation of 5-LO to the nuclear membrane. In patients with asthma, following 4 weeks of dietary soy isoflavone supplementation, ex vivo eosinophil LTC4 synthesis decreased by 33% (N=11, P=0.02) and FENO decreased by 18% (N=13, P=0.03). Conclusion: At physiologically relevant concentrations, genistein inhibits eosinophil LTC4 synthesis in vitro, probably by blocking p38- and MAPKAP-2-dependent activation of 5-LO. In asthma patients, dietary soy isoflavone supplementation reduces eosinophil LTC4 synthesis and eosinophilic airway inflammation. These results support a potential role for soy isoflavones in the treatment of asthma.

Original languageEnglish (US)
Pages (from-to)103-112
Number of pages10
JournalClinical and Experimental Allergy
Volume38
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • 5-lipoxygenase
  • Asthma
  • Eosinophils
  • Genistein
  • Soy isoflavones

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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