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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/158738
Título

Serotonin drives the acquisition of a profibrotic and anti-inflammatory gene profile through the 5-HT7RPKA signaling axis

AutorDomínguez-Soto, Ángeles ; Usategui, Alicia; Casas-Engel, Mateo de las ; Simón-Fuentes, Miriam; Nieto, Concha ; Cuevas, Víctor D.; Vega, Miguel A. ; Pablos, J. L.; Corbí, Angel L.
Fecha de publicación7-nov-2017
EditorNature Publishing Group
CitaciónScIentIfIc Reports 7: 14761 (2017)
ResumenPeripheral serotonin (5-hydroxytryptamine, 5-HT) regulates cell growth and differentiation in numerous cell types through engagement of seven types of cell surface receptors (HTR1–7). Deregulated 5-HT/ HTR levels contribute to pathology in chronic inflammatory diseases, with macrophages being relevant targets for the physio-pathological effects of 5-HT. In fact, 5-HT skews human macrophage polarization through engagement of 5-HT2BR and 5-HT7R receptors. We now report that 5-HT primes macrophages for reduced pro-inflammatory cytokine production and IFN type I-mediated signaling, and promotes an anti-inflammatory and pro-fibrotic gene signature in human macrophages. The acquisition of the 5-HT-dependent gene profile primarily depends on the 5-HT7R receptor and 5-HT7R-initiated PKAdependent signaling. In line with the transcriptional results, 5-HT upregulates TGFβ1 production by human macrophages in an HTR7- and PKA-dependent manner, whereas the absence of Htr7 in vivo results in diminished macrophage infiltration and collagen deposition in a mouse model of skin fibrosis.Our results indicate that the anti-inflammatory and pro-fibrotic activity of 5-HT is primarily mediated through the 5-HT7R-PKA axis, and that 5-HT7R contributes to pathology in fibrotic diseases.
Descripción15 p.-6 fig.-1 tab.
Versión del editorhttp://dx.doi.org/10.1038/s41598-017-15348-y
URIhttp://hdl.handle.net/10261/158738
DOI10.1038/s41598-017-15348-y
ISSN2045-2322
E-ISSN2045-2322
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