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Serotonin receptor 5-HT7 modulates inflammatory-associated functions of macrophages.

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Titel: Serotonin receptor 5-HT7 modulates inflammatory-associated functions of macrophages.
Autoren: Bahr, Frauke S., Müller, Franziska E., Kasten, Martina, Benen, Nils, Sieve, Irina, Scherr, Michaela, Falk, Christine S., Hilfiker-Kleiner, Denise, Ricke-Hoch, Melanie, Ponimaskin, Evgeni
Quelle: Cellular & Molecular Life Sciences; 1/21/2025, Vol. 82 Issue 1, p1-19, 19p
Schlagwörter: CENTRAL nervous system, MEDICAL sciences, PHAGOCYTOSIS, SEROTONIN receptors, THERAPEUTICS, MACROPHAGES
Abstract: The hormone and neurotransmitter serotonin regulates numerous physiological functions within the central nervous system and in the periphery upon binding to specific receptors. In the periphery, the serotonin receptor 7 (5-HT7R) is expressed on different immune cells including monocytes and macrophages. To investigate the impact of 5-HT7R-mediated signaling on macrophage properties, we used human THP-1 cells and differentiated them into pro-inflammatory M1- and anti-inflammatory M2-like macrophages. Pharmacological 5-HT7R activation with the specific agonist LP-211 especially modulates morphology of M1-like macrophages by increasing the number of rounded cells. Furthermore, 5-HT7R stimulation results in significantly reduced phagocytic and migratory ability of M1-like macrophages. Noteworthy, LP-211 treatment leads to changes in secretory properties of all macrophage types with the highest effects obtained for M0- and M2c-like macrophages. Finally, the importance of 5-HT7R for regulation of phagocytosis was confirmed in human primary CD14+ cells. These results indicate that 5-HT7R activation selectively impairs basic functions of macrophages and might thus be a new access point for the modulation of macrophage responses in the future treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]
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Datenbank: Complementary Index
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Abstract:The hormone and neurotransmitter serotonin regulates numerous physiological functions within the central nervous system and in the periphery upon binding to specific receptors. In the periphery, the serotonin receptor 7 (5-HT7R) is expressed on different immune cells including monocytes and macrophages. To investigate the impact of 5-HT7R-mediated signaling on macrophage properties, we used human THP-1 cells and differentiated them into pro-inflammatory M1- and anti-inflammatory M2-like macrophages. Pharmacological 5-HT7R activation with the specific agonist LP-211 especially modulates morphology of M1-like macrophages by increasing the number of rounded cells. Furthermore, 5-HT7R stimulation results in significantly reduced phagocytic and migratory ability of M1-like macrophages. Noteworthy, LP-211 treatment leads to changes in secretory properties of all macrophage types with the highest effects obtained for M0- and M2c-like macrophages. Finally, the importance of 5-HT7R for regulation of phagocytosis was confirmed in human primary CD14<sup>+</sup> cells. These results indicate that 5-HT7R activation selectively impairs basic functions of macrophages and might thus be a new access point for the modulation of macrophage responses in the future treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]
ISSN:1420682X
DOI:10.1007/s00018-024-05570-z