Vasoactive intestinal peptide (VIP) has been shown to affect the proliferative activity of human keratinocytes in vitro. In our present study, we investigated whether VIP affects early events of keratinocyte migration, i.e. the formation of pseudopodia-like protrusions and the zeta-potential which was assessed by the electrophoretic mobility (EM). Under optimal culture conditions (10% fetal calf serum supplement; FCS) VIP changed the total percentage of migrating HaCaT cells by increasing the Ki67-negative portion. Migration was maximally stimulated in the range of 10(-9) M VIP (+121.1%) and 10(-7) M VIP (+78.9%). Under suboptimal conditions (i.e. 2% FCS or serum free medium) low concentrations of VIP (10(-7) M to 10(-13) M VIP) decreased spontaneous migration up to 70%. The EM of pooled normal keratinocytes (0.59 +/- 0.018 mu/s/V/cm) was slightly increased by Phe6-Leu17-VIP and more markedly by VIP in a dose-dependent manner. Our observations suggest a modulatory effect of VIP on early events of human keratinocyte migration in vitro. These findings might be of importance for spontaneous migration within the epidermal compartment both under physiological conditions and in wound healing.
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