Selective Incorporation of Hetes into Epidermal Phospholipids

Abstract

The skin has an active lipid metabolism and is capable of producing a variety of eicosanoids (Ruzicka and Printz, 1984). Recently, there has been particular attention directed toward the existence of epidermal lipoxygenase products and their possible role in cutaneous inflammation (Voorhees, 1983; Camp and Cunningham, 1988). This interest began with the discovery that the lesions of certain chronic inflammatory skin disorders (e.g. psoriasis and atopic dermatitis) are associated with an imbalance of lipoxygenase products, specifically elevated levels of pro-inflammatory leukotriene B₄ (LTB₄), a 5-lipoxygenase product of leukocytes (Grabbe et al., 1984; Brain et al., 1984; Ruzicka et al., 1986). Interestingly, the major lipoxygenase product of keratinocytes (the predominant epidermal cell-type) is the 15-lipoxygenase product 15-hydroxyeicosatetraenoic acid (15-HETE) (Burrall et al., 1985; Nugteren and Kivits, 1987), an inhibitor of 5--lipoxygenase activity in vitro (Vanderhoek et al., 1982). The potential of epidermally-derived 15-HETE to attenuate 5-lipoxygenase activity has led to speculation that there may be a local deficit of 15-HETE in lesional tissues which may in turn result in a decreased ability to limit the generation of 5-lipoxygenase products by infiltrating leukocytes. In support of this hypothesis, intralesional injections of 15-HETE have been used to clear psoriatic lesions (Fogh et al., 1988). Furthermore, certain dietary oils that result in elevated in vivo levels of epidermal 15-lipoxygenasejproducts (Miller et al., 1990; Miller et al., 1991) have been shown to be clinically effective in the treatment of psoriasis and other chronic inflammatory skin disorders (Ziboh et al., 1986; Maurice et al., 1987; Wright and Burton, 1982).