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Antiinflammatory effects of genistein, a tyrosine kinase inhibitor, on a guinea pig model of asthma
journal contributionposted on 2003-01-15, 00:00 authored by Wei DuanWei Duan, I C Kuo, S Selvarajan, K Y Chua, B H Bay, W S F Wong
Protein tyrosine kinase signaling cascade plays a pivotal role in the activation of inflammatory cells. The purpose of this study was to investigate the effects of genistein, a broad-spectrum protein tyrosine kinase inhibitor, on airway inflammation in an in vivo guinea pig model of asthma. Guinea pigs were actively sensitized by intraperitoneal injections of ovalbumin. Aerosolized ovalbumin induced acute bronchoconstriction in conscious animals in a dose-dependent manner. Genistein (15 mg/kg given intraperitoneally) markedly inhibited ovalbumin-induced, but not histamine- and methacholine-induced, acute bronchoconstriction. In addition, genistein significantly reduced ovalbumin-induced increases in total cell counts and eosinophils recovered in bronchoalveolar lavage fluid, airway eosinophilia, and eosinophil peroxidase activity in cell-free bronchoalveolar lavage fluid and markedly attenuated ovalbumin-induced airway hyperresponsiveness to inhaled methacholine. Immunoblot analysis of lung lysates isolated from genistein-pretreated animals showed that epidermal growth factor-induced tyrosine phosphorylation in lung tissues was inhibited by genistein. These results implicate that inhibition of tyrosine kinase signaling cascade may have therapeutic potential for allergic airway inflammation.
JournalAmerican journal of respiratory and critical care medicine
Pagination185 - 192
PublisherAmerican Thoracic Society
LocationNew York, N.Y.
Publication classificationC1.1 Refereed article in a scholarly journal
Copyright notice2003, American Thoracic Society
CategoriesNo categories selected
inflammationovalbuminairway hyperresponsivenessbronchoalveolar lavage fluidmethacholineAnalysis of VarianceAnimalsAsthmaBlotting, WesternBronchiBronchial HyperreactivityDexamethasoneDisease Models, AnimalEnzyme InhibitorsGenisteinGuinea PigsImmunohistochemistryInjections, IntraperitonealMaleMethacholine ChlorideProbabilityRandom AllocationReference ValuesTracheaTreatment Outcome