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A mechanism of benefit of soy genistein in asthma: inhibition of eosinophil p38-dependent leukotriene synthesis.
| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kalhan, R. Smith, L. J. Nlend, M. C. Nair, A. Hixon, J. L. Sporn, P. H. S. |
| Description | Country affiliation: United States Author Affiliation: Kalhan R ( Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. r-kalhan@northwestern.edu) |
| 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 C(4) (LTC(4)) 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 LTC(4) 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 (FE(NO)) and ex vivo eosinophil LTC(4) production were assessed before and after the soy isoflavone treatment period. RESULTS: Genistein inhibited eosinophil LTC(4) synthesis (IC(50) 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 LTC(4) synthesis decreased by 33% (N=11, P=0.02) and FE(NO) decreased by 18% (N=13, P=0.03). CONCLUSION: At physiologically relevant concentrations, genistein inhibits eosinophil LTC(4) synthesis in vitro, probably by blocking p38- and MAPKAP-2-dependent activation of 5-LO. In asthma patients, dietary soy isoflavone supplementation reduces eosinophil LTC(4) synthesis and eosinophilic airway inflammation. These results support a potential role for soy isoflavones in the treatment of asthma. |
| File Format | HTM / HTML |
| ISSN | 09547894 |
| e-ISSN | 13652222 |
| Journal | Clinical & Experimental Allergy |
| Issue Number | 1 |
| Volume Number | 38 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2008-01-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Discipline Immunology Asthma Metabolism Eosinophils Drug Effects Genistein Pharmacology Leukotrienes Biosynthesis Soybeans Chemistry P38 Mitogen-activated Protein Kinases Adolescent Arachidonate 5-lipoxygenase Diet Therapy Immunology Pathology Cell Survival Cells, Cultured Dietary Supplements Cytology Mitogen-activated Protein Kinase 1 Mitogen-activated Protein Kinase 3 Phosphorylation Pilot Projects Clinical Trial Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
