Peroxisome proliferator-activated receptor-β/δ modulates mast cell phenotype

Abstract

The peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is known to have multiple anti-inflammatory effects, typically observed in endothelial cells, macrophages, T cells and B cells. Despite the fact that mast cells are important mediators of inflammation, to date, the role of PPARβ/δ in mast cells has not been examined. Hence, the present study examined the hypothesis that PPARβ/δ modulates mast cell phenotype. Bone-marrowderived mast cells (BMMCs) and peritoneal mast cells from Pparβ/δ+/+mice expressed higher levels of high-affinity IgE receptor (FceRI) compared with Pparβ/δ_/_mice. BMMCs from Pparβ/δ+/+mice also exhibited dense granules, associated with higher expression of enzymes and proteases compared with Pparβ/δ_/_mice. Resting BMMCs from Pparβ/δ+/+mice secreted lower levels of inflammatory cytokines, associated with the altered activation of phospholipase Cγ1 and extracellular signal-regulated kinases compared with Pparβ/δ_/_mice. Moreover, the production of cytokines by mast cells induced by various stimuli was highly dependent on PPARβ/δ expression. This study demonstrates that PPARβ/δ is an important regulator of mast cell phenotype.