Role of PPARgamma in inflammatory response related to mast cells

Abstract

The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily and ligand-activated transcription factors. The activation of PPARgamma regulates lipid and glucose homeostasis and its agonists have been developed as novel antidiabetic drugs. Recently, it has been reported that PPARgamma plays roles in inflammatory and immunological responses. Especially in monocyte/macrophage system, the expression of PPARgamma and the negative regulation of cytokine production has been reported. Mast cells are derived from stem cells in bone marrow, and their proliferation and differentiation are regulated by stimulation of stem cell factor from fibroblasts and/or IL-3 from T lymphocytes. Recently, it was reported that PPARgamma is expressed in mast cells, but its roles remain uncertain. After antigen stimulation, mast cells produce and release prostaglandin D(2) which is metabolized to 15-deoxy Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)). Because 15d-PGJ(2) acts potently as an endogenous PPARgamma agonist, mast cells might play roles in inflammation and immunological responses via the PPARgamma pathway. In this paper we will discuss PPARgamma function in mast cells using cultured bone marrow derived mast cells obtained from heterozygous PPARgamma-deficient mice.