Ciglitazone inhibits the antigen-induced leukotrienes production independently of PPARγ in RBL-2H3 mast cells

Peroxisome prolifelator-activated receptor gamma (PPAR gamma) is a ligand-activated transcription factor, through which PPAR gamma 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 PPAR gamma. Previously, we showed that a PPAR gamma agonist, troglitazone, inhibited cycteinyl (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 PPAR gamma. A PPAR gamma agonist, ciglitazone, significantly inhibited Cys-leukotrienes, but not prostaglandin D-2, production. The inhibition was not attenuated by the pretreatment with a PPAR gamma antagonist. Ciglitazone did not alter the mRNA expression of acyl-coenzyme A binding protein, the gene expression of which is up-regulated by PPAR gamma, nor induce the nucleus translocation of PPAR gamma. These results suggest that the inhibition by PPAR-y agonists of Cys-leukotrienes production in RBL-2H3 cells after IgE receptor triggering is not through the activation of PPAR gamma. (c) 2005 Elsevier B.V. All rights reserved.