THE NEUROHORMONE MELATONIN INHIBITS CYTOKINE, MITOGEN AND IONIZING-RADIATION INDUCED NF-KAPPA-B

Recently, the neurohormone melatonin was found to be a potent endogeno us hydroxyl radical scavenger. Since the activation of an important tr anscriptional regulator, nuclear factor-kappa B (NF-kappa B) involves free radicals as second messengers, we investigated whether melatonin alters NF-kappa B expression if present during treatment of HeLa S3 ce lls with known activators. The results show that upon treatment of HeL a Si cells with tumor necrosis factor-alpha or phorbol 12-myristate 13 -acetate, or with ionizing radiation, there is a profound induction of NF-kappa B binding activity. If present at the time of treatment, exo genously added melatonin, at a concentration as low as 10 mu M, was fo und to inhibit the activation of NF-kappa B by these agents. This resu lt leads to the hypothesis that melatonin can play a role in many phys iological functions through its modulation of NF-kappa B (and possibly other) transcriptional regulators.