Enzyme association with PPARgamma: evidence of a new role for 15-lipoxygenase type 2

Fatty acids have historically important structural roles in contributing to epidermal barrier function and therefore cutaneous health. Their metabolism to bioactive compounds is often up-regulated in response to cutaneous toxins thus providing them with functional roles. Some metabolites of arachidonic acid, such as 15S-hydroxyeicosatetraenoic acid (HETE), also serve functional roles as direct ligands for peroxisome proliferator activated receptors (PPARs). 15S-HETE, produced by 15-lipoxygenase type 2 (15-LOX-2), is an endogenous ligand for PPARgamma. This report demonstrates epidermal keratinocyte expression of both 15-LOX-2 and PPARgamma and provides evidence for a relationship beyond that of ligand-producer and -user, namely in vivo association of the two proteins at the molecular level making the enzyme a candidate nuclear receptor coregulator. Such close physical approximation of the 15S-HETE-producing enzyme and PPARgamma could potentiate the receptor response to a short-lived ligand. 15-LOX-2 may exemplify a class of enzymatically active nuclear receptor coactivator proteins distinct from those previously described but sharing their ability to promote expression from nuclear receptor-regulated promoters.