| First Author | Huang JT | Year | 1999 |
| Journal | Nature | Volume | 400 |
| Issue | 6742 | Pages | 378-82 |
| PubMed ID | 10432118 | Mgi Jnum | J:200339 |
| Mgi Id | MGI:5508298 | Doi | 10.1038/22572 |
| Citation | Huang JT, et al. (1999) Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase. Nature 400(6742):378-82 |
| abstractText | The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-dependent nuclear receptor that has been implicated in the modulation of critical aspects of development and homeostasis, including adipocyte differentiation, glucose metabolism and macrophage development and function. PPAR-gamma is activated by a range of synthetic and naturally occurring substances, including antidiabetic thiazolidinediones, polyunsaturated fatty acids, 15-deoxy-delta prostaglandin J2 and components of oxidized low-density lipoprotein, such as 13-hydroxyoctadecadienoic acid (13-HODE) and 15-hydroxyeicosatetraenoic acid (15-HETE). However, the identities of endogenous ligands for PPAR-gamma and their means of production in vivo have not been established. In monocytes and macrophages, 13-HODE and 15-HETE can be generated from linoleic and arachidonic acids, respectively, by a 12/15-lipoxygenase that is upregulated by the TH2-derived cytokine interleukin-4. Here we show that interleukin-4 also induces the expression of PPAR-gamma and provide evidence that the coordinate induction of PPAR-gamma and 12/15-lipoxygenase mediates interleukin-4-dependent transcription of the CD36 gene in macrophages. These findings reveal a physiological role of 12/15-lipoxygenase in the generation of endogenous ligands for PPAR-gamma, and suggest a paradigm for the regulation of nuclear receptor function by cytokines. |
