Function of oleic acid on epidermal barrier and calcium influx into keratinocytes is associated withN-methyl d-aspartate-type glutamate receptors

Background Unsaturated fatty acids from sebum affect calcium dynamics in epidermal keratinocytes, disrupt the barrier function and induce abnormal keratinization. However, the mechanisms of these effects have not been clarified. Objectives To investigate the function of unsaturated fatty acids in epidermis. Methods Antagonists of calcium channel receptors were applied to mouse skin together with oleic acid. Measurements were made of transepidermal water loss (TEWL), and hyperproliferation was assessed. The effects of the antagonists on calcium influx into cultured normal human keratinocytes and on cytokine production were also evaluated. Results N‐methyl‐d‐aspartate (NMDA) receptor antagonists such as MK801 and D‐AP5 specifically inhibited the increase in TEWL caused by oleic acid, and suppressed keratinocyte hyperproliferation. These compounds also inhibited the increase in the intracellular concentration of calcium ions induced by oleic acid. MK801 suppressed the production of interleukin‐1α by keratinocytes induced by oleic acid. Conclusions Unsaturated fatty acids such as oleic acid might function via NMDA receptors.