Possible Involvement of the Inhibition of NF-κB Factor in Anti-Inflammatory Actions That Melatonin Exerts on Mast Cells

• Published in: Journal of cellular biochemistry 2016-08, Vol.117 (8), p.1926-1933
• Main Authors: Maldonado, M.D., García-Moreno, H., González-Yanes, C., Calvo, J.R.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Calcimycin - toxicity; Cell Line, Tumor; CYTOKINES; INFLAMMATION; Interleukin-6 - immunology; Mast Cells - immunology; MELATONIN; Melatonin - pharmacology; NF-kappa B - immunology; NF-κB; Rats; RBL-2H3 MAST CELLS; Signal Transduction - drug effects; Signal Transduction - immunology; Tetradecanoylphorbol Acetate - toxicity; Tumor Necrosis Factor-alpha - immunology
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.25491

ABSTRACT Melatonin is a molecule endogenously produced in a wide variety of immune cells, including mast cells (RBL‐2H3). It exhibits immunomodulatory, anti‐inflammatory and anti‐apoptotic properties. The physiologic mechanisms underlying these activities of melatonin have not been clarified in mast cells. This work is designed to determine the anti‐inflammatory effect and mechanism of action of melatonin on activated mast cells. RBL‐2H3 were pre‐treated with exogenous melatonin (MELx) at physiological (100nM) and pharmacological (1 mM) doses for 30 min, washed and activated with PMACI (phorbol 12‐myristate 13‐acetate plus calcium ionophore A23187) for 2 h and 12 h. The data shows that pre‐treatment of MELx in stimulated mast cells, significantly reduced the levels of endogenous melatonin production (MELn), TNF‐α and IL‐6. These effects are directly related with the MELx concentration used. MELx also inhibited IKK/NF‐κB signal transduction pathway in stimulated mast cells. These results indicate a molecular basis for the ability of melatonin to prevent inflammation and for the treatment of allergic inflammatory diseases through the down‐regulation of mast cell activation. J. Cell. Biochem. 117: 1926–1933, 2016. © 2016 Wiley Periodicals, Inc. This study reveals that PMACI induces the activation of NF‐κB and causes an inflammatory toxicity on mast cells, which could be mitigated by MELx. This mitigation is shown by the improvement of cell viability and the decrease of TNF‐α, IL‐6 and MELn levels.