Melanocyte-stimulating properties of proinflammatory chemical mediators.

Skin darkening after cutaneous inflammation is a well known phenomenon but its mechanisms for this hyperpigmentation have not been clarified yet. Because in inflamed skin various mediators such as arachidonic acid metabolites and histamine are found in increased amounts, we have studied their effects on cultured normal human melanocytes. As reported previously we have found that prostaglandine E2 stimulated normal human melanocytes. In addition histamine, platelet activating factor, bradykinin and arachidonic acid metabolites such as leukotriene (LT) C4 and LTD4 also stimulated melanocytes.They were found to increase the total amounts of immunoreactive tyrosinase and tyrosinase related protein, the number of dendrites and the size of melanocytes. In these proinflammatory mediators, LTC4 and histamine showed far strong stimulatory effect. On the other hand, serotonin, heparin and other arachidonic acid metabolites such as PGE1 PGFs and 12-hydroxy eicosatetraenoic acid (12-HETE) did not show any significant stimulatory effect.Present studies suggest that various proinflammatory chemical mediators, especially LTC4 and histamine are involved in the stimulation of melanocytes to accelerate the production of melanine and its active transfer to neighboring keratinocytes, resulting into the formation of hyperpigmentation after skin inflammation.