Retinoid modulation of phorbol ester effects in skin

This chapter reviews convenient assay methods for retinoids against phorbol ester-induced effects in the skin. The chapter describes methods for measuring 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced edema, ornithine decarboxylase (ODC) activity, and DNA synthesis. Measurements of TPA-induced ear edema, ODC activity, and DNA synthesis provide convenient methods to assess the effects of retinoids on phorbol ester-mediated events in the skin. The antiinflammatory effects of retinoids in the TPA ear edema model may be due to their action as inhibitors of arachidonic acid metabolism, all-trans-Retinoic acid and 13-cis-retinoic acid are reported to act as inhibitors of snake venom phospholipase A2 and to inhibit the release and metabolism of arachidonic acid in calcium ionophore-stimulated rat peritoneal macrophages. In TPAtreated mouse skin, phospholipase A2 activity is elevated and would provide a source of free arachidonic acid for metabolism into prostaglandin E2 (PGE2)and 15-hydroxyeicosatetraenoic acids (HETE).