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International Immunology Advance Access originally published online on March 31, 2005
International Immunology 2005 17(5):599-606; doi:10.1093/intimm/dxh242
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org

5-Hydroxytryptamine modulates cytokine and chemokine production in LPS-primed human monocytes via stimulation of different 5-HTR subtypes

Thorsten Dürk1, Elisabeth Panther2, Tobias Müller1, Stephan Sorichter1, Davide Ferrari3, Cinzia Pizzirani3, Francesco Di Virgilio3, Daniel Myrtek1, Johannes Norgauer4 and Marco Idzko1

1 Department of Pneumology and 2 Department of Gastroenterology, University Medical Clinic, University of Freiburg, D-79106 Freiburg i. Br., Germany
3 Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation University of Ferrara, I-44100 Ferrara, Italy
4 Department of Dermatology, University of Jena, D-07740 Jena, Germany

Correspondence to: M. Idzko; E-mail: idzko{at}med1.ukl.uni-freiburg.de

The neurotransmitter 5-hydroxytryptamine (5-HT), commonly known as serotonin, is released at peripheral sites from activated enterochromaffin cells, mast cells and platelets. In this study we analyzed the biological activity and intracellular signaling of 5-HT in human monocytes. By reverse transcription (RT) and PCR, messenger RNA (mRNA) expression of 5-HT receptor 1E (5-HTR1E), 5-HTR2A, 5-HTR3, 5-HTR4 and 5-HTR7 could be revealed. Functional studies showed that 5-HT modulates the release of IL-1ß, IL-6, IL-8/CXCL8, IL-12p40 and tumor necrosis factor-{alpha} (TNF-{alpha}), while it has no effect on the production of IL-18 and IFN-{gamma} in LPS-stimulated human blood monocytes. Moreover, RT and PCR revealed that 5-HT modulated mRNA levels of IL-6 and IL-8/CXCL8, but did not influence mRNA levels of IL-1ß and TNF-{alpha}. Pharmacological studies with isotype-selective receptor agonists allowed us to show that 5-HTR3 subtype up-regulates the LPS-induced production of IL-1ß, IL-6 and IL-8/CXCL8, while it was not involved in TNF-{alpha} and IL-12p40 secretion. Furthermore, activation of the Gs-coupled 5-HTR4 and 5-HTR7 subtypes increased intracellular cyclic AMP (cAMP) and secretion of IL-1ß, IL-6, IL-12p40 and IL-8/CXCL8, while, on the contrary, it inhibited LPS-induced TNF-{alpha} release. Interestingly, 5-HTR1 and 5-HTR2 agonists did not modulate the LPS-induced cytokine production in human monocytes. Our results point to a new role for 5-HT in inflammation by modulating cytokine production in monocytes via activation of 5-HTR3, 5-HTR4 and 5-HTR7 subtypes.

Keywords: IL-1ß, IL-6, IL-8/CXCL8, monocytes, serotonin

Transmitting editor: M. Reth


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