β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/19/8/2182 |
| _version_ | 1811325105393893376 |
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| author | Marco A. Pires-Lapa Claudia E. Carvalho-Sousa Erika Cecon Pedro A. Fernandes Regina P. Markus |
| author_facet | Marco A. Pires-Lapa Claudia E. Carvalho-Sousa Erika Cecon Pedro A. Fernandes Regina P. Markus |
| author_sort | Marco A. Pires-Lapa |
| collection | DOAJ |
| description | 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 β-adrenoceptors in pinealocytes is the main route for triggering melatonin synthesis. However, despite the well-known role of β-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 β-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 β-adrenoceptors promotes the synthesis of melatonin by stimulating cyclic AMP/protein kinase A (PKA) pathway and by activating the nuclear translocation of NF-κB. 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. |
| first_indexed | 2024-04-13T14:27:11Z |
| format | Article |
| id | doaj.art-628f2a2cd35f43d2a637d2097a1c0c11 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T14:27:11Z |
| publishDate | 2018-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-628f2a2cd35f43d2a637d2097a1c0c112022-12-22T02:43:16ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-07-01198218210.3390/ijms19082182ijms19082182β-Adrenoceptors Trigger Melatonin Synthesis in PhagocytesMarco A. Pires-Lapa0Claudia E. Carvalho-Sousa1Erika Cecon2Pedro A. Fernandes3Regina P. Markus4Laboratory of Chronopharmacology, Deartment of Physiology, Institute of Bioscience, University of São Paulo, 05508-900 São Paulo, BrazilLaboratory of Chronopharmacology, Deartment of Physiology, Institute of Bioscience, University of São Paulo, 05508-900 São Paulo, BrazilLaboratory of Chronopharmacology, Deartment of Physiology, Institute of Bioscience, University of São Paulo, 05508-900 São Paulo, BrazilLaboratory of Neuroimmunoendocrinology, Department of Physiology, Institute of Bioscience, University of São Paulo, 05508-900 São Paulo, BrazilLaboratory of Chronopharmacology, Deartment of Physiology, Institute of Bioscience, University of São Paulo, 05508-900 São Paulo, BrazilMelatonin (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 β-adrenoceptors in pinealocytes is the main route for triggering melatonin synthesis. However, despite the well-known role of β-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 β-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 β-adrenoceptors promotes the synthesis of melatonin by stimulating cyclic AMP/protein kinase A (PKA) pathway and by activating the nuclear translocation of NF-κB. 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.http://www.mdpi.com/1422-0067/19/8/2182melatoninmacrophagesbeta-adrenergic receptorsimmune-pineal axisnuclear factor kappa B (NF-κB)extra-pineal melatonin synthesis |
| spellingShingle | Marco A. Pires-Lapa Claudia E. Carvalho-Sousa Erika Cecon Pedro A. Fernandes Regina P. Markus β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes International Journal of Molecular Sciences melatonin macrophages beta-adrenergic receptors immune-pineal axis nuclear factor kappa B (NF-κB) extra-pineal melatonin synthesis |
| title | β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes |
| title_full | β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes |
| title_fullStr | β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes |
| title_full_unstemmed | β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes |
| title_short | β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes |
| title_sort | β adrenoceptors trigger melatonin synthesis in phagocytes |
| topic | melatonin macrophages beta-adrenergic receptors immune-pineal axis nuclear factor kappa B (NF-κB) extra-pineal melatonin synthesis |
| url | http://www.mdpi.com/1422-0067/19/8/2182 |
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