12(S)-HETE is the stereospecific hydroxy product from the reduction of 12(S)-hydroperoxyeicosatetraenoic acid [12(S)-HETE], which itself is a 12-lipoxygenase metabolite of arachidonic acid. 12(S)-HETE has been shown to be chemotactic and chemokinetic for polymorphonuclear leukocytes and vascular smooth muscle cells. It also acts as a second messenger in angiotensin-II induced aldosterone production. Evidence also suggests that 12(S)-HETE is involved in suppressing renin production, stimulating insulin secretion by pancreatic tissue, and inducing endothelial cell retraction and tumor cell adhesion.
15(S)-HETE is the major hydroxy derivative of arachidonic acid when acted upon by 15-lipoxygenase (15-LOX). It is also the primary monohydroxy acid synthesized by the lipoxygenase activity of Cyclooxygenase-1 (COX-1). Interleukin 4 has been shown to regulate 15(S)-HETE expression and incorporation into cellular phospholipids. 15(S)-HETE binds to actin and the alpha subunit of mitochondrial ATP synthase suggesting a more direct method in regulating some physiological activities. Increased levels of 15(S)-HETE are associated with asthma, rhinitis, chronic paranasal sinusitis and rheumatoid arthritis.