EICOSAPENTAENOIC ACID-INDUCED CHANGES IN MEMBRANE FLUIDITY AND CELL-ADHESION MOLECULES IN CULTURED HUMAN KERATINOCYTES

The effects of eicosapentaenoic acid (EPA, 20:5n-3) on the lipid dynam ics of cultured epidermal keratinocytes and their expression of cell a dhesion molecules were investigated, and were compared with those of a rachidonic acid (AA, 20:4n-6), When keratinocytes were treated with 3 mu g/ml of EPA or AA for 72 h, these compounds were found to be incorp orated 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 cell ular content of n-6 arachidonic acid. These changes in fatty acid comp osition 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) cm(2)/s untreated to 2.23 +/- 0.35 x l0(-8) cm(2)/s EPA-trea ted (P < 0.001), and 2.16 +/- 0.35 x 10(-8) cm(2)/s AA-treated (P < 0. 001)]. Intercellular adhesion molecule-1 (ICAM-1) was induced on the k eratinocyte membrane in the presence of tumour necrosis factor-alpha a nd interferon-gamma, and pretreatment with EPA or AA further enhanced the expression, almost to an equal degree, as estimated by now cytomet ry (P < 0.05), These results indicate that the modulation of ICAM-1 ex pression does not seem to be EPA-specific, but is presumably a consequ ence of increased membrane fluidity due to the increased levels of uns aturated fatty acids of both the n-3 and n-6 series in the membrane.