Abstract
Melatonin is a highly conserved molecule found in prokaryotes and eukaryotes that acts as the darkness hormone, translating environmental lighting to the whole body, and as a moderator of innate and acquired defense, migration, and cell proliferation processes. This review evaluates the importance of pineal activity in monitoring PAMPs and DAMPs and in mounting an inflammatory response or innate immune response. Activation of the immune–pineal axis, which coordinates the pro-and anti-inflammatory phases of an innate immune response, is described. PAMPs and DAMPs promote the immediate suppression of melatonin production by the pineal gland, which allows leukocyte migration. Monocyte-derived macrophages, important phagocytes of microbes, and cellular debris produce melatonin locally and thereby initiate the anti-inflammatory phase of the acute inflammatory response. The role of locally produced melatonin in organs that directly contact the external environment, such as the skin and the gastrointestinal and respiratory tracts, is also discussed. In this context, as resident macrophages are self-renewing cells, we explore evidence indicating that, besides avoiding overreaction of the immune system, extra-pineal melatonin has a fundamental role in the homeostasis of organs and tissues.
Highlights
Health is based on active and constant vigilance to detect pathogens, dead cells, and cellular matrix disruption
Right side: PAMPs and DAMPs activate their receptors in pinealocytes, inducing the nuclear translocation of the NFκB dimer p50/p50, which blocks Snat transcription and melatonin synthesis
The nat-κB1, which induces the transcription of Snat, binds only subunits containing cRel, while nat-κB2, which blocks transcription, binds to other subunits, including p50/p50. These results provided the molecular basis for understanding the opposite responses of pinealocytes and macrophages/microglia to acute inflammatory stimuli and the biological basis underneath the time interval between suppressing the nocturnal pineal melatonin synthesis and the beginning of the synthesis of melatonin by activated macrophages
Summary
Health is based on active and constant vigilance to detect pathogens, dead cells, and cellular matrix disruption. The understanding of the molecular pathways inside the cells and molecular signals for the integration of information inside tissues and between organs was developed during the 20th century. Nowadays, based on molecular and cellular mechanisms, we are exploring system biology approach to disclose temporal and spatial integration in physiological, pathophysiological, and pathological conditions. We will discuss the switching of melatonin sources from the pineal gland to activated macrophages during the development of an innate immune response and the role of resident macrophages as an extra-pineal source. This new idea offers the potential to tailor the pharmacological use of melatonin and to develop biomarkers based on melatonin sources
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
