Ciglitazone inhibits the antigen-induced leukotrienes production independently of PPARgamma in RBL-2H3 mast cells.
Peroxisome prolifelator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor, through which PPARgamma agonists have been demonstrated to down-regulate inflammatory cell functions. Recently, the agonists are reported to exert, in some conditions, their inhibitory actions independently of PPARgamma. Previously, we showed that a PPARgamma agonist, troglitazone, inhibited cysteinyl (Cys)-leukotrienes production in RBL-2H3 cells after IgE receptor triggering. Here we examined whether the inhibition of cycteinyl-leukotrienes production in the cells was dependent on the activation of PPARgamma. A PPARgamma agonist, ciglitazone, significantly inhibited Cys-leukotrienes, but not prostaglandin D2, production. The inhibition was not attenuated by the pretreatment with a PPARgamma antagonist. Ciglitazone did not alter the mRNA expression of acyl-coenzyme A binding protein, the gene expression of which is up-regulated by PPARgamma, nor induce the nucleus translocation of PPARgamma. These results suggest that the inhibition by PPARgamma agonists of Cys-leukotrienes production in RBL-2H3 cells after IgE receptor triggering is not through the activation of PPARgamma.
Okuyama
Kaori
K
Department of Pathophysiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Sendai 981-8558, Japan.
Yamashita
Masamichi
M
Kitabatake
Yuki
Y
Kawamura
Shunsuke
S
Takayanagi
Motoaki
M
Ohno
Isao
I
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003545:Cysteine / Q000096:biosynthesis; D015777:Eicosanoids / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D015289:Leukotrienes / Q000096:biosynthesis*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
D000214:Acyl Coenzyme A; D000941:Antigens; D002352:Carrier Proteins; D015777:Eicosanoids; D015289:Leukotrienes; D047495:PPAR gamma; D012333:RNA, Messenger; D017455:Receptors, IgE; D045162:Thiazolidinediones; C112381:cysteinyl-leukotriene; D003545:Cysteine; C039671:ciglitazone