Regulation of macrophage gene expression by the peroxisome proliferator-activated receptor-γ

The peroxisome proliferator-activated receptor-γ (PPAR-γ), which is a member of the nuclear hormone receptor superfamily and was originally shown to play an important role in adipocyte differentiation and glucose homeostasis, is now known to regulate cellular proliferation and inflammatory responses. A range of synthetic and naturally occurring substances activates PPAR-γ, however the identities of endogenous ligands for PPAR-γand their means of production in vivo have not been well established. In monocytes and macrophages, interleukin-4 (IL-4) increases the expression of 12/15-lipoxygenase and thus13-HODE and 15-HETE production. We show that IL-4 induces the expression of PPAR-γ and provide evidence that the coordinate induction of PPAR-γ and 12/15-lipoxygenase mediates IL-4 dependent transcription of the CD36 gene and down-regulation of iNOS in macrophages. These findings suggest that PPAR-γ activity may play an important role in mediating macrophage gene expression signaled by IL-4.