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.

The expression of mRNA for calcitonin gene-related peptide receptors in a mucosal type mast cell line, RBL-2H3.

Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) belong to a calcitonin-family of regulatory peptides. Receptors for CGRP and ADM have been suggested to be present on both mucosal (MMC) and connective tissue (CTMC) type of mast cells, based on histamine release by these peptides. Recently, it was reported that mRNA for ADM receptors, but not for CGRP receptors, was expressed in rat peritoneal mast cells, a representative of type CTMC. However, mRNA expression for the receptors in MMC has not been studied yet. Therefore, we examined whether mRNAs encoding CGRP or ADM receptor subunit, RDC-1, calcitonin receptor-like receptor (CRLR), and receptor activity-modifying proteins (RAMPs) are present, and if so, whether their expression is modified by IgE receptor triggering, in a mucosal type mast cell line, rat basophilic leukemia (RBL-2H3) cells using RT-PCR. RBL-2H3 cells constitutively express mRNA for RDC-1, CRLR, RAMP3 but not that for RAMP1 and RAMP2, and IgE receptor triggering was shown neither to induce the gene expression of RAMP1 and RAMP2, nor to enhance that of RDC-1, CRLR or RAMP3. These results indicate that RBL-2H3 cells posses receptors for both CGRP and ADM, suggesting various functions of these peptides in physiological and pathophysiological conditions where mast cells of the mucosal type are involved.