Inhibition by troglitazone of the antigen-induced production of leukotrienes in immunoglobulin E-sensitized RBL-2H3 cells

1 The effect of troglitazone, an anti-diabetic drug with insulin-sensitizin g 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)-specif ic immunoglobulin E (IgE)-sensitized RBL-2H3 mast cells following stimulati on by the antigen, DNP-conjugated human serum albumin. Levels of LTB4, C-4 and E-4 and PGD(2) in the conditioned medium were enzyme-immunoassayed. 2 Troglitazone inhibited the antigen-induced production of LTB4, C-4 and E- 4 and the potency of the inhibition was comparable to that of zileuton, a s pecific inhibitor of 5-lipoxygenase (5-LOX) and a clinically used anti-asth matic drug. Neither troglitazone nor zileuton affected antigen-induced prod uction of PGD(2), arachidonic acid release from membrane phospholipids and degranulation. 3 Troglitazone inhibited LTB4 production by the supernatant fraction of RBL -2H3 cell lysate with similar potency to zileuton, suggesting that troglita zone inhibits LT production by direct inhibition of 5-LOX activity. 4 Furthermore, it was shown that troglitazone as well as zileuton inhibited LTB4 production in A23187-stimulated rat peritoneal neutrophils. 5 These findings suggest that troglitazone inhibits antigen-induced LT prod uction in the IgE-sensitized RBL-2H3 cells and A23187-stimulated rat perito neal neutrophils by direct inhibition of 5-LOX activity.