期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 14, 期 6, 页码 10979-10997出版社
MDPI AG
DOI: 10.3390/ijms140610979
关键词
immune-pineal axis; nuclear factor kappa B-NF-kappa B; melatonin; pineal gland; innate immune response; glucocorticoid; macrophage
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo-FAPESP [2007/07871-6, 2011/50198-6]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [07/07871-6] Funding Source: FAPESP
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.-light-chain-enhancer of activated B cells (NF-kappa B) blocks noradrenaline-induced melatonin synthesis in pinealocytes, which induces melatonin synthesis in macrophages. In addition, melatonin reduces NF-kappa B 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-kappa B activity leads these cells to a more quiescent state. The opposite effect of NF-kappa B in pinealocytes and immune competent cells is due to different NF-kappa B dimers recruited in each phase of the defense response. This coordinated shift of the source of melatonin driven by NF-kappa B 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.
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