The high-affinity IgE receptor FcepsilonRI 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 FcepsilonRI expression in human basophilic KU812 cells was studied. The PPARalpha ligand, leukotriene B-4, did not affect the cell surface expression of FcepsilonRI. However, prostaglandin (PG) A(1) and 15-deoxy-Delta(12,14) PGJ(2) (15d-PGJ(2)), which are PPARbeta and 7 ligands, respectively, were both able to decrease FcepsilonRI expression. Treatment with PGA(1) or 15d-PGJ(2) separately also reduced histamine release from KU812 cells in response to cross-linkage of FcepsilonRI. In addition, RT-PCR analysis showed that KU812 cells expressed the mRNA for PPARalpha, beta, and gamma, indicating that PPARbeta or gamma may negatively regulate the cell activation via FcepsilonRI. Cells treated with 15d-PGJ(2) expressed lower levels of FcepsilonRIalpha and gamma mRNA, and PGA(1) treatment decreased the level of FcepsilonRIgamma mRNA. These results suggest that the suppression of FcepsilonRI expression by PPARs may be due to the down-regulation of FcepsilonRIalpha or gamma mRNA. (C) 2002 Elsevier Science (USA). All rights reserved.