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001-es BibID:	BIBFORM054457
035-os BibID:	Article ID: e106533
Első szerző:	Szabó Attila (molekuláris biológus, immunológus, filozófus)
Cím:	Psychedelic N,N-Dimethyltryptamine and 5-Methoxy- N,N-Dimethyltryptamine Modulate Innate and Adaptive Inflammatory Responses through the Sigma-1 Receptor of Human Monocyte-Derived Dendritic Cells / Attila Szabo, Attila Kovacs, Ede Frecska, Eva Rajnavolgyi
Dátum:	2014
ISSN:	1932-6203
Megjegyzések:	The orphan receptor sigma-1 (sigmar-1) is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. Since the details of these findings have not been elucidated so far, we studied the effects of the endogenous sigmar-1 ligands N,N-dimethyltryptamine (NN-DMT), its derivative 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and the synthetic high affinity sigmar-1 agonist PRE-084 hydrochloride on human primary monocyte-derived dendritic cell (moDCs) activation provoked by LPS, polyI:C or pathogen-derived stimuli to induce inflammatory responses. Co-treatment of moDC with these activators and sigma-1 receptor ligands inhibited the production of pro-inflammatory cytokines IL-1?, IL-6, TNF? and the chemokine IL-8, while increased the secretion of the anti-inflammatory cytokine IL-10. The T-cell activating capacity of moDCs was also inhibited, and dimethyltryptamines used in combination with E. coli or influenza virus as stimulators decreased the differentiation of moDC-induced Th1 and Th17 inflammatory effector T-cells in a sigmar-1 specific manner as confirmed by gene silencing. Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via sigmar-1 that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the CNS or peripheral tissues. Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban psychedelics N,N-dimethyltryptamine 5-methoxy-N,N-dimethyltryptamine sigma-1 receptor innate immunity inflammation dendritic cell
Megjelenés:	Plos One. - 9 : 8 (2014), [12] p. -
További szerzők:	Kovács Attila Frecska Ede (1953-) (pszichiáter) Rajnavölgyi Éva (1950-) (immunológus)
Pályázati támogatás:	4.2.4. A/2-11-1-2012-0001 TÁMOP
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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