The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation induced NF-kappa B.
Recently, the neurohormone melatonin was found to be a potent endogenous hydroxyl radical scavenger. Since the activation of an important transcriptional 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 cells with known activators. The results show that upon treatment of HeLa S3 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, exogenously added melatonin, at a concentration as low as 10 microM, was found to inhibit the activation of NF-kappa B by these agents. This results leads to the hypothesis that melatonin can play a role in many physiological functions through its modulation of NF-kappa B (and possibly other) transcriptional regulators.
Mohan
N
N
Department of Radiology, University of Texas Health Science Center, San Antonio 78284-7800, USA.
Sadeghi
K
K
Reiter
R J
RJ
Meltz
M L
ML
D001483:Base Sequence; D006367:HeLa Cells; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000096:biosynthesis* / Q000187:drug effects / Q000528:radiation effects; D011839:Radiation, Ionizing; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D008550:Melatonin; D013755:Tetradecanoylphorbol Acetate