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Published ahead of print on October 24, 2002, doi:10.1164/rccm.200205-420OC
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American Journal of Respiratory and Critical Care Medicine Vol 167. pp. 185-192, (2003)
© 2003 American Thoracic Society

Original Article

Antiinflammatory Effects of Genistein, a Tyrosine Kinase Inhibitor, on a Guinea Pig Model of Asthma

Wei Duan, I. Chun Kuo, Sathiyamoorthy Selvarajan, Kaw Yan Chua, Boon Huat Bay and W. S. Fred Wong

Departments of Pharmacology, Paediatrics, and Anatomy, Faculty of Medicine, National University of Singapore, Republic of Singapore

Correspondence and requests for reprints should be addressed to W. S. Fred Wong, Ph.D., Department of Pharmacology Faculty of Medicine, National University of Singapore MD2 18 Medical Drive, Singapore 117597. E-mail: phcwongf{at}nus.edu.sg

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.

Key Words: inflammation • ovalbumin • airway hyperresponsiveness • bronchoalveolar lavage fluid • methacholine




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