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

Eur J Pharmacol. 2005 Oct 3;521(1-3):21-8. doi: 10.1016/j.ejphar.2005.08.010. Epub 2005 Sep 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Acyl Coenzyme A / metabolism
  • Animals
  • Antigens / immunology
  • Antigens / pharmacology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cysteine / biosynthesis
  • Eicosanoids / biosynthesis
  • Gene Expression / drug effects
  • Immunohistochemistry
  • Leukotrienes / biosynthesis*
  • Mast Cells / drug effects
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • PPAR gamma / agonists
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, IgE / metabolism
  • Thiazolidinediones / pharmacology*

Substances

  • Acyl Coenzyme A
  • Antigens
  • Carrier Proteins
  • Eicosanoids
  • Leukotrienes
  • PPAR gamma
  • RNA, Messenger
  • Receptors, IgE
  • Thiazolidinediones
  • cysteinyl-leukotriene
  • Cysteine
  • ciglitazone