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Int. J. Mol. Sci. 2013, 14(6), 10979-10997; doi:10.3390/ijms140610979
Review

Immune-Pineal Axis: Nuclear Factor κB (NF-kB) Mediates the Shift in the Melatonin Source from Pinealocytes to Immune Competent Cells

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Received: 14 March 2013; in revised form: 3 May 2013 / Accepted: 13 May 2013 / Published: 24 May 2013
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Abstract: Pineal gland melatonin is the darkness hormone, while extra-pineal melatonin produced by the gonads, gut, retina, and immune competent cells acts as a paracrine or autocrine mediator. The well-known immunomodulatory effect of melatonin is observed either as an endocrine, a paracrine or an autocrine response. In mammals, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) blocks noradrenaline-induced melatonin synthesis in pinealocytes, which induces melatonin synthesis in macrophages. In addition, melatonin reduces NF-κB activation in pinealocytes and immune competent cells. Therefore, pathogen- or danger-associated molecular patterns transiently switch the synthesis of melatonin from pinealocytes to immune competent cells, and as the response progresses melatonin inhibition of NF-κB activity leads these cells to a more quiescent state. The opposite effect of NF-κB in pinealocytes and immune competent cells is due to different NF-κB dimers recruited in each phase of the defense response. This coordinated shift of the source of melatonin driven by NF-κB is called the immune-pineal axis. Finally, we discuss how this concept might be relevant to a better understanding of pathological conditions with impaired melatonin rhythms and hope it opens new horizons for the research of side effects of melatonin-based therapies.
Keywords: immune-pineal axis; nuclear factor κB—NF-κB; melatonin; pineal gland; innate immune response; glucocorticoid; macrophage immune-pineal axis; nuclear factor κB—NF-κB; melatonin; pineal gland; innate immune response; glucocorticoid; macrophage
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Markus, R.P.; Cecon, E.; Pires-Lapa, M.A. Immune-Pineal Axis: Nuclear Factor κB (NF-kB) Mediates the Shift in the Melatonin Source from Pinealocytes to Immune Competent Cells. Int. J. Mol. Sci. 2013, 14, 10979-10997.

AMA Style

Markus RP, Cecon E, Pires-Lapa MA. Immune-Pineal Axis: Nuclear Factor κB (NF-kB) Mediates the Shift in the Melatonin Source from Pinealocytes to Immune Competent Cells. International Journal of Molecular Sciences. 2013; 14(6):10979-10997.

Chicago/Turabian Style

Markus, Regina P.; Cecon, Erika; Pires-Lapa, Marco A. 2013. "Immune-Pineal Axis: Nuclear Factor κB (NF-kB) Mediates the Shift in the Melatonin Source from Pinealocytes to Immune Competent Cells." Int. J. Mol. Sci. 14, no. 6: 10979-10997.


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