Inhibitory effects of glucocorticoids on rat eosinophil superoxide generation and chemotaxis.
Eosinophil infiltration into inflammatory tissues and the subsequent release of inflammatory mediators are the hallmarks of several inflammatory allergic diseases. Although there have been a considerable number of publications on anti-inflammatory effects of glucocorticoids, little is known about whether glucocorticoids affect the activation of eosinophils directly. We studied the effects of three glucocorticoids, mometasone furoate, dexamethasone and beclomethasone dipropionate, on superoxide generation and the chemotaxis of rat eosinophils. Highly purified rat eosinophils were treated for 6 h with mometasone furoate, dexamethasone or beclomethasone dipropionate. Eosinophils were stimulated with phorbol myristate acetate (PMA) for superoxide generation, while for induction of chemotaxis, platelet-activating factor (PAF) or leukotriene B(4) (LTB(4)) was used. None of the glucocorticoids used in the present study caused significant suppressive effects on superoxide generation induced by PMA. On the other hand, both PAF- and LTB(4)-induced migration of rat eosinophils were inhibited in a concentration-dependent manner by glucocorticoids. Mometasone furoate showed a significant effect at concentrations higher than 10(-11) M. Dexamethasone and beclomethasone dipropionate also caused a significant inhibition at concentrations higher than 10(-8) and 10(-7) M, respectively. These results indicated that the anti-inflammatory effects of glucocorticoids were mediated by direct inhibition of eosinophil migration. Furthermore, mometasone furoate was suggested to be more useful than the other drugs in the treatment of allergic diseases responsible for eosinophil chemotaxis.
Sugimoto
Yukio
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, 700-8530, Okayama, Japan.
Ogawa
Masami
M
Tai
Nobuyuki
N
Kamei
Chiaki
C
D000818:Animals; D001507:Beclomethasone / Q000494:pharmacology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007958:Leukocyte Count; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D000068656:Mometasone Furoate; D010972:Platelet Activating Factor / Q000494:pharmacology; D011244:Pregnadienediols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005938:Glucocorticoids; D010972:Platelet Activating Factor; D011244:Pregnadienediols; D000068656:Mometasone Furoate; D013481:Superoxides; D007975:Leukotriene B4; D003907:Dexamethasone; D001507:Beclomethasone; D013755:Tetradecanoylphorbol Acetate