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

Immunology. 2017 Apr;150(4):456-467. doi: 10.1111/imm.12699. Epub 2017 Jan 24.

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-marrow-derived mast cells (BMMCs) and peritoneal mast cells from Pparβ/δ+/+ mice expressed higher levels of high-affinity IgE receptor (FcεRI) 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.

Keywords: bone marrow-derived mast cells; cytokine; inflammation; peroxisome proliferator-activated receptor-β/δ.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Bone Marrow Cells / physiology*
  • Cell Differentiation*
  • Cells, Cultured
  • Cytokines / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Inflammation Mediators / metabolism
  • Mast Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • PPAR delta / genetics
  • PPAR delta / metabolism*
  • PPAR-beta / genetics
  • PPAR-beta / metabolism*
  • Phenotype
  • Receptors, IgE / genetics
  • Receptors, IgE / metabolism
  • Signal Transduction / genetics

Substances

  • Cytokines
  • Inflammation Mediators
  • PPAR delta
  • PPAR-beta
  • Receptors, IgE
  • Extracellular Signal-Regulated MAP Kinases