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

International Journal of Molecular Sciences

Regina P Markus¹  Erika Cecon¹ 

关键词: immune-pineal axis;    nuclear factor κB—NF-κB;    melatonin;    pineal gland;    innate immune response;    glucocorticoid;    macrophage;   

DOI  :  10.3390/ijms140610979

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland