12-Hydroxyeicosatetraenoic acid (12-HETE) is a chemotactic stimulus for epidermal cells

Abstract

Several observations point to an important role of 12HETE and LTB4 in cutaneous physiology and in the pathophysiology of inflammatory skin diseases, in particular psoriasis [13]. Normal epidermal cells possess a high capacity for the transformation of arachidonic acid (AA) into 12-HETE by 12-1ipoxygenase. It is the main eicosanoid which is generated in epidermal homogenates besides PGE2 and P G D 2 [9, 14]. In contrast, the 5lipoxygenase product LTB4 is formed mainly by leukocytes [4] which infiltrate skin during inflammation. In psoriasis, highly elevated concentrations of 12-HETE are found in lesional skin [2, 8]. In addition, 12-HETE and LTB4 are chemoattractants for PMNLs which could contribute to the infiltration of PMNLs in psoriatic skin and other cutaneous inflammatory reactions [3, 6]. Although the metabolic processes which lead to the formation of 12-HETE in skin are well understood, the exact function of this AA-metabolite in cutaneous biology is not clear. Growth stimulation of keratinocytes by 12-HETE was reported by Kragballe and Fallon [11], but has not been confirmed by other groups [7, 12]. Here we report a novel aspect of 12-HETE and LTB 4 in cutaneous biology. We detected a chemotactic response of epidermal cells towards 12-Sand 12-R-HETE as well as LTB4. The response of the cells towards 12-HETE was in the range of the KD of a high affinity 12-HETE receptor described recently by our group [7]. Eicosanoids (12-S-HETE, 12-R-HETE, LTB4) were supplied by Paesel (Frankfurt/Main, FRG) as free acids in ethanol. The ethanol was evaporated under nitrogen immediately before use, and the eicosanoids were dissolved in serum-free DMEM to the required concentration. EGF was purchased from Sebak (Aidenbach, FRG). Fibroblast-conditioned medium (FCM) was pre-