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J.Health Sci., 53(4), 389-396, 2007
Mechanism of the Inhibitory Effect of Tranexamic Acid on Melanogenesis in Cultured Human Melanocytes in the Presence of Keratinocyte-conditioned Medium
Kazuhisa Maeda*, a, 1 and Yasushi Tomitab
aLife Science Research Center, Shiseido Co., Ltd., 2-12-1 Fukuura, Kanazawa-ku, Yokohama 236-8643, Japan and
bDepartment of Dermatology, Graduate School of Medicine, Nagoya University, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan
Tranexamic acid (TA) reduces hyperpigmentation in melasma patients, but the mechanism of its action is unknown. We have investigated the action of TA in human melanocyte cultures with or without keratinocyte-conditioned medium (KCM). In melanocyte cultures without KCM, TA in the concentration range of 0.5 mM to 5 mM did not reduce the activity of tyrosinase, a key enzyme of melanin synthesis, whereas it reduced the tyrosinase activity in the presence of KCM. These results indicate that TA inhibits melanin synthesis of melanocytes not by acting directly on melanocytes, but by inhibiting melanocyte activators contained in KCM. In fractionation studies of KCM, the stimulatory activity was predominantly contained in the fractions with an apparent molecular weight of 54000. Inhibition of the urokinase-type plasminogen activator (uPA) in KCM with specific anti-uPA antibody significantly decreased the KCM-induced increase of tyrosinase activity and inhibited the KCM-induced morphological changes of melanocytes. Our results suggest that TA inhibits melanin synthesis in melanocytes by interfering with the interaction of melanocytes and keratinocytes through inhibition of the plasminogen/plasmin system.
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