TY - JOUR
T1 - Inhibition by troglitazone of the antigen-induced production of leukotrienes in immunoglobulin E-sensitized RBL-2H3 cells
AU - Yamashita, Masamichi
AU - Kushihara, Mikie
AU - Hirasawa, Noriyasu
AU - Takasaki, Wataru
AU - Takahagi, Hidekuni
AU - Takayanagi, Motoaki
AU - Ohuchi, Kazuo
PY - 2000
Y1 - 2000
N2 - 1. The effect of troglitazone, an anti-diabetic drug with insulin-sensitizing action, on antigen-induced production of leukotriene (LT) B4, C4 and E4 and prostaglandin D2 (PGD2) 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 LTB4, C4 and E4 and PGD2 in the conditioned medium were enzyme-immunoassayed. 2. Troglitazone inhibited the antigen-induced production of LTB(4,) C4 and E4 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 PGD2, 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 troglitazone 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 production in the IgE-sensitized RBL-2H3 cells and A23187-stimulated rat peritoneal neutrophils by direct inhibition of 5-LOX activity.
AB - 1. The effect of troglitazone, an anti-diabetic drug with insulin-sensitizing action, on antigen-induced production of leukotriene (LT) B4, C4 and E4 and prostaglandin D2 (PGD2) 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 LTB4, C4 and E4 and PGD2 in the conditioned medium were enzyme-immunoassayed. 2. Troglitazone inhibited the antigen-induced production of LTB(4,) C4 and E4 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 PGD2, 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 troglitazone 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 production in the IgE-sensitized RBL-2H3 cells and A23187-stimulated rat peritoneal neutrophils by direct inhibition of 5-LOX activity.
KW - 5-Lipoxygenase
KW - Degranulation
KW - Leukotriene
KW - RBL-2H3 cell
KW - Troglitazone
KW - Zileuton
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U2 - 10.1038/sj.bjp.0703044
DO - 10.1038/sj.bjp.0703044
M3 - Article
C2 - 10694244
AN - SCOPUS:0033960111
VL - 129
SP - 367
EP - 373
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 2
ER -