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Inhibition by troglitazone of the antigen‐induced production of leukotrienes in immunoglobulin E‐sensitized RBL‐2H3 cells
Author(s) -
Yamashita Masamichi,
Kushihara Mikie,
Hirasawa Noriyasu,
Takasaki Wataru,
Takahagi Hidekuni,
Takayanagi Motoaki,
Ohuchi Kazuo
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703044
Subject(s) - troglitazone , zileuton , chemistry , leukotriene c4 , antigen , immunoglobulin e , prostaglandin d2 , potency , pharmacology , arachidonate 5 lipoxygenase , endocrinology , prostaglandin , leukotriene , medicine , antibody , biochemistry , arachidonic acid , immunology , biology , in vitro , enzyme , peroxisome , asthma , gene
The effect of troglitazone, an anti‐diabetic drug with insulin‐sensitizing action, on antigen‐induced production of leukotriene (LT) B 4 , C 4 and E 4 and prostaglandin D 2 (PGD 2 ) was examined in dinitrophenol (DNP)‐specific immunoglobulin E (IgE)‐sensitized RBL‐2H3 mast cells following stimulation by the antigen, DNP‐conjugated human serum albumin. Levels of LTB 4 , C 4 and E 4 and PGD 2 in the conditioned medium were enzyme‐immunoassayed. Troglitazone inhibited the antigen‐induced production of LTB 4 , C 4 and E 4 and the potency of the inhibition was comparable to that of zileuton, a specific inhibitor of 5‐lipoxygenase (5‐LOX) and a clinically used anti‐asthmatic drug. Neither troglitazone nor zileuton affected antigen‐induced production of PGD 2 , arachidonic acid release from membrane phospholipids and degranulation. Troglitazone inhibited LTB 4 production by the supernatant fraction of RBL‐2H3 cell lysate with similar potency to zileuton, suggesting that troglitazone inhibits LT production by direct inhibition of 5‐LOX activity. Furthermore, it was shown that troglitazone as well as zileuton inhibited LTB 4 production in A23187‐stimulated rat peritoneal neutrophils. These findings suggest that troglitazone inhibits antigen‐induced LT production in the IgE‐sensitized RBL‐2H3 cells and A23187‐stimulated rat peritoneal neutrophils by direct inhibition of 5‐LOX activity.British Journal of Pharmacology (2000) 129 , 367–373; doi: 10.1038/sj.bjp.0703044