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

Peroxisome Proliferator Activated Receptor Ligands as Regulators of Airway Inflammation and Remodelling in Chronic Lung Disease

“…PPAR α ligands had no effect on cytokine release or Fc ε RI expression in these human cells [26, 61]. Although fenofibrate, Wy14 643, and CGZ inhibited antigen-induced leukotriene production from rat basophilic leukemia (RBL)-2H3 cells, these effects are likely to be PPAR-independent since PPAR α mRNA was below detection [34] and the inhibition by CGZ was not prevented by a PPAR γ antagonist or associated with nuclear translocation of the receptor [62]. However, proliferation of bone-marrow derived murine mast cells was increased by RGZ in an apparently PPAR γ -dependent manner, since it was prevented by the PPAR γ antagonist GW9662 and the effect of RGZ was reduced in cells from PPAR γ +/− mice [50].…”

PPARα/γ‐Independent Effects of PPARα/γ Ligands on Cysteinyl Leukotriene Production in Mast Cells

“…The inhibitory effects of troglitazone on these LTs are strong and similar to those of the clinically-used 5-LOX inhibitor zileuton (1 μ M) [17]. Another PPAR γ ligand, ciglitazone (30 μ M), also inhibits LTC 4 production [18]. Neither troglitazone nor ciglitazone affects hexosaminidase release, the index for mast cell degranulation, or prostaglandin D 2 production via cyclooxygenase [17, 18].…”

“…Another PPAR γ ligand, ciglitazone (30 μ M), also inhibits LTC 4 production [18]. Neither troglitazone nor ciglitazone affects hexosaminidase release, the index for mast cell degranulation, or prostaglandin D 2 production via cyclooxygenase [17, 18]. The observations that 0.1 μ M of the PPAR γ antagonist GW9662, which inhibits the PPAR γ activation of (AOx) 3 -TK-Luc promoter induced by the PPAR γ ligand rosiglitazone [19], did not affect LTC 4 production [18] and that 30 μ M of GW9662 inhibits LTC 4 production (our unpublished data) in the IgE-sensitized, and Ag-treated RBL-2H3 mast cell line obscures the contribution of PPAR γ on LT production in mast cells.…”

“…We have observed that the immunoreactivity of anti-PPAR γ IgG in the RBL-2H3 mast cell line though ciglitazone (30 μ M) does not induce the mRNA level of acyl-CoA binding protein [18], which is a target gene of PPAR γ [22]. Diaz et al [23] have examined PPAR γ protein in mouse BMMCs by SDS-PAGE immunoblot analysis and reported that the amount of PPAR γ in BMMCs is equivalent to that in the Jurkat T-cell line, which is known to have effective PPAR γ [24].…”

“…The PPAR α and γ ligands were preincubated for 2 hours before antigen treatment in mast cells [13, 17, 18], and the decrease of Fc ε RI on the surface of mast cells is not the main mechanism of the PPAR-independent inhibition of cysLT production. Regulation of the sensitivity to antigens is of pathological interest in allergic diseases, including asthma, and the interaction of mast cells with other inflammatory cells in pathological conditions should be examined.…”