Eicosapentaenoic acid-induced changes in membrane fluidity and cell adhesion molecules in cultured human keratinocytes

Abstract

The effects of eicosapentaenoic acid (EPA, 20:5n-3) on the lipid dynamics of cultured epidermal keratinocytes and their expression of cell adhesion molecules were investigated, and were compared with those of arachidonic acid (AA, 20:4n-6). When keratinocytes were treated with 3 micrograms/ml of EPA or AA for 72 h, these compounds were found to be incorporated into the cells. EPA-induced lipid changes were distinguished by a significant increase in the cellular content of n-3 polyunsaturated fatty acids, whereas AA treatment resulted in an increase in the cellular content of n-6 arachidonic acid. These changes in fatty acid composition were accompanied by an increase in cellular membrane fluidity, which was evaluated by the diffusion coefficient, using the method of fluorescence recovery after photobleaching (FRAP) [from 1.77 +/- 0.34 x 10(-8) cm2/s untreated to 2.23 +/- 0.35 x 10(-8) cm2/s EPA-treated (P < 0.001), and 2.16 +/- 0.35 x 10(-8) cm2/s AA-treated (P < 0.001)]. Intercellular adhesion molecule-1 (ICAM-1) was induced on the keratinocyte membrane in the presence of tumour necrosis factor-alpha and interferon-gamma, and pretreatment with EPA or AA further enhanced the expression, almost to an equal degree, as estimated by flow cytometry (P < 0.05). These results indicate that the modulation of ICAM-1 expression does not seem to be EPA-specific, but is presumably a consequence of increased membrane fluidity due to the increased levels of unsaturated fatty acids of both the n-3 and n-6 series in the membrane.