beta-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes

Author(s)

Pires-Lapa, Marco A. ; Carvalho-Sousa, Claudia E. ; Cecon, Erika ; Fernandes, Pedro A. ; Markus, Regina P.

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 19, n. 8, p. 13-pg., 2018-08-01.

Abstract

Melatonin (5-methoxy-N-acetylserotonin), the pineal hormone, is also synthesized by immune-competent cells. The pineal hormone signals darkness, while melatonin synthesized on demand by activated macrophages at any hour of the day acts locally, favoring regulatory/tolerant phenotypes. Activation of beta-adrenoceptors in pinealocytes is the main route for triggering melatonin synthesis. However, despite the well-known role of beta-adrenoceptors in the resolution macrophage phenotype (M2), and the relevance of macrophage synthesized melatonin in facilitating phagocytic activity, there is no information regarding whether activation of beta-adrenoceptors would induce melatonin synthesis by monocytes. Here we show that catecholamines stimulate melatonin synthesis in bone marrow-derived dendritic cells and RAW 264.7 macrophages. Activation of beta-adrenoceptors promotes the synthesis of melatonin by stimulating cyclic AMP/protein kinase A (PKA) pathway and by activating the nuclear translocation of NF-kappa B. Considering the great number of macrophages around sympathetic nerve terminals, and the relevance of this system for maintaining macrophages in stages compatible to low-grade inflammation, our data open the possibility that extra-pineal melatonin acts as an autocrine/paracrine signal in macrophages under resolution or tolerant phenotypes. (AU)

• FAPESP's process: 09/17923-9 - Pineal gland as a target for B-amyloid peptide
• Grantee: Erika Cecon
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/13691-1 - Immune-pineal axis: time-niology integrated to surveillance and defense
• Grantee: Regina Pekelmann Markus
• Support Opportunities: Research Projects - Thematic Grants