Peroxisome proliferator-activated receptor-/ modulates mast cell phenotype

摘要

The peroxisome proliferator-activated receptor-/ (PPAR/) 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 PPAR/ in mast cells has not been examined. Hence, the present study examined the hypothesis that PPAR/ modulates mast cell phenotype. Bone-marrow-derived mast cells (BMMCs) and peritoneal mast cells from Ppar/(+/+) mice expressed higher levels of high-affinity IgE receptor (Fc epsilon RI) compared with Ppar/(-/-) mice. BMMCs from Ppar/(+/+) mice also exhibited dense granules, associated with higher expression of enzymes and proteases compared with Ppar/(-/-) mice. Resting BMMCs from Ppar/(+/+) mice secreted lower levels of inflammatory cytokines, associated with the altered activation of phospholipase C1 and extracellular signal-regulated kinases compared with Ppar/(-/-) mice. Moreover, the production of cytokines by mast cells induced by various stimuli was highly dependent on PPAR/ expression. This study demonstrates that PPAR/ is an important regulator of mast cell phenotype.