Microvascular endothelial cells are an important source of proinflammatory cytokines as well as chemokines and mediate leukocyte-endothelial interactions during cutaneous inflammation via the expression of cell adhesion molecules. Recent studies revealed a crucial role of neuropeptide such as α melanocyte stimulating hormone (αMSH) within the skin immunsystem. αMSH is generated by posttranslational enzymatic cleavage of the procursor molecule proopiomelanocortin (POMC). There are six receptors known, that are capable to bind one or more POMC-derived peptides, the melanocortin receptor type 1-5 (MC 1-5) and the ACTH-receptor. In contrast to the other receptors, MC-1 is specific for αMSH only. The purpose of the present study was to investigate the melanocortin receptor expression in human dermal microvascular endothelial cells (HMEC-1) by performing RT-PCR using melanocortin receptor specific primepairs. Accordingly, unstimulated HMEC-1 cells were found to express MC-1 and its expression was increased upon stimulation with IL-1β and αMSH. In addition, IL-1β stimulated HMEC-1 cells but not unstimulated cells expressed also MC-4. Neither in unstimulated nor IL-1β, PMA, αMSH or UVB stimulated cells MC-2 or MC-3 could be detected. In order to evaluate the physiological relevance of the MC-1 expression, HMEC-1 were treated with various concentrations of αMSH (10 - 6 - 10 - 5 M) and investigated for IL-8 release using a specific ELISA. αMSH (10 - 1 0 - 10 - 1 2 M) after 5-24hr significantly upregulated IL-8 production by HMEC-1. These data provide first evidence that microvascular endothelial cells express functional melanocortin receptors which may play a role in inflammation.