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

The peroxisome proliferator-activated receptor-gamma (PPAR-gamma), which is a member of the nuclear hormone receptor superfamily and was originally sh own to play an important role in adipocyte differentiation and glucose home ostasis, is now known to regulate cellular proliferation and inflammatory r esponses, A range of synthetic and naturally occurring substances activates PPAR-gamma, however the identities of endogenous ligands for PPAR-gamma an d their means of production in vivo have not been well established. In mono cytes 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 i nduces the expression of PPAR-gamma and provide evidence that the coordinat e induction of PPAR-gamma and 12/15-lipoxygenase mediates IL-4 dependent tr anscription of the CD36 gene and down-regulation of iNOS in macrophages. Th ese findings suggest that PPAR-gamma activity may play an important role in mediating macrophage gene expression signaled by IL-4. Copyright (C) 2001 S. Karger AG, Basel.