Peroxisome proliferator-activated receptor ligands negatively regulate the expression of the high-affinity IgE receptor FcεRI in human basophilic KU812 cells

The high-affinity IgE receptor FcεRI is expressed on the cell surface of mast cells and basophils, and plays a central role in IgE-mediated inflammatory reactions. Recently, peroxisome proliferator-activated receptors (PPARs) have been implicated in the anti-inflammatory response. To investigate a possible role for PPAR in human basophils, the effect of PPAR ligands on FcεRI expression in human basophilic KU812 cells was studied. The PPARα ligand, leukotriene B₄, did not affect the cell surface expression of FcεRI. However, prostaglandin (PG) A₁ and 15-deoxy-Δ^12,14 PGJ₂ (15d-PGJ₂), which are PPARβ and γ ligands, respectively, were both able to decrease FcεRI expression. Treatment with PGA₁ or 15d-PGJ₂ separately also reduced histamine release from KU812 cells in response to cross-linkage of FcεRI. In addition, RT-PCR analysis showed that KU812 cells expressed the mRNA for PPARα, β, and γ, indicating that PPARβ or γ may negatively regulate the cell activation via FcεRI. Cells treated with 15d-PGJ₂ expressed lower levels of FcεRIα and γ mRNA, and PGA₁ treatment decreased the level of FcεRIγ mRNA. These results suggest that the suppression of FcεRI expression by PPARs may be due to the down-regulation of FcεRIα or γ mRNA.