Context
Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear hormone receptor family of transcription factors. It is able to both activate and repress transcription, and is reported to negatively regulate macrophage function. Ligands for PPARγ include anti-diabetic thiazolidinedione drugs, and various metabolites of arachidonic and linoleic acids (AA and LA). Whilst the addition of exogenous PPARγ-activating ligands can block the expression of proinflammatory gene products such as inducible nitric oxide synthase (iNOS), interleukin-1α (IL-1α) and IL-6 in macrophages, the source and identity of endogenous PPARγ ligands are not known. A 12/15-lipoxygenase (LOX) is induced by IL-4 treatment of macrophages, and is able to metabolise AA or LA to form PPARγ ligands. However, the role of this enzyme in the regulation of macrophage gene expression is not yet known. To investigate the production of PPARγ-activating ligands in cells of the myeloid lineage, and the role of these ligands in the regulation of gene expression.