Arachidonic acid transformations in normal and psoriatic skin

Abstract

The levels of free arachidonic acid and 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) are elevated in lesional epidermis of psoriasis (Hammarstrom et al: Proc. Natl. Acad. Sci., USA 72:5130-5134, 1975). In the present study, transformations of arachidonic acid by normal and psoriatic involved and uninvolved epidermis were qualitatively compared with similar transformations in adult mouse epidermis and dermis and neonatal mouse keratinocyte suspensions. Metabolites were identified by mass spectrometry or by comigration with reference compounds on thin-layer chromatography. Human epidermis and mouse dermis converted arachidonic acid mainly to 12-HETE and prostaglandin E2. Mouse epidermis, formed HETE, PGD2 and PGE2. The keratinocyte suspensions formed the same products as mouse epidermis but also PGF (2α). Cultures of these cells exhibited stimulated synthesis of PGE2 in response to tetradecanoyl phorbol acetate. This stimulation was prevented by triamcinolone, indomethacin and 5,8,11,14-eicosatetraynoic acid (ETA) but not by 5,8,11-eicosatriynoic acid (ETI). The latter compound stimulated basal PGE2 formation. In conclusion: the tissues investigated all converted arachidonic acid to HETE and PGE2, thromboxane B2 and 6-keto-PGF(1α) were not formed in appreciable amounts under the conditions used; which might suggest that HETE, PGE2, PGF(2α) and their precursors are more likely to be regulators of epidermal function than thromboxane A2 or PGI2; and finally, cultured keratinocytes which produce HETE, PGE2 and PGF(2α) may be a suitable model for detailed studies of growth regulation by arachidonic acid metabolites.