Antiinflammatory effects of genistein, a tyrosine kinase inhibitor, on a guinea pig model of asthma.
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.
Duan
Wei
W
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Republic of Singapore.
Kuo
I Chun
IC
Selvarajan
Sathiyamoorthy
S
Chua
Kaw Yan
KY
Bay
Boon Huat
BH
Wong
W S Fred
WS
D000704:Analysis of Variance; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D015153:Blotting, Western; D001980:Bronchi / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D016210:Methacholine Chloride; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D014132:Trachea / Q000473:pathology; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D016210:Methacholine Chloride; D003907:Dexamethasone; D019833:Genistein