The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation induced NF-κB

Recently, the neurohormone melatonin was found to be a potent endogenous hydroxyl radical scavenger. Since the activation of an important transcriptional regulator, nuclear factor-κB (NF-κB) involves free radicals as second messengers, we investigated whether melatonin alters NF-κB expression if present during treatment of HeLa S3 cells with known activators. The results show that upon treatment of HeLa S3 cells with tumor necrosis factor-α or phorbol 12-myristate 13-acetate, or with ionizing radiation, there is a profound induction of NF-κB binding activity. If present at the time of treatment, exogenously added melatonin, at a concentration as low as 10 μM, was found to inhibit the activation of NF-κB by these agents. This result leads to the hypothesis that melatonin can play a role in many physiological functions through its modulation of NF-κB (and possibly other) transcriptional regulators.