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001-es BibID:BIBFORM072832
035-os BibID:(Cikkazonosító)1765 (WOS)000423430000013 (Scopus)85041329100
Első szerző:Szabó Attila (molekuláris biológus, immunológus, filozófus)
Cím:Immunomodulatory capacity of the serotonin receptor 5-HT2B in a subset of human dendritic cells / Szabo Attila, Gogolak Peter, Koncz Gabor, Foldvari Zsofia, Pazmandi Kitti, Miltner Noemi, Poliska Szilard, Bacsi Attila, Djurovic Srdjan, Rajnavolgyi Eva
Dátum:2018
ISSN:2045-2322
Megjegyzések:Serotonin is a monoamine neurotransmitter that signals through a wide array of receptors (5-HT1-7) many of which are also involved in immune processes. Dendritic cells (DCs) are crucial players in immune defense by bridging innate and adaptive immune responses via their vast repertoire of pattern recognition receptors and antigen-presenting capability. Although serotonin is known to influence immunity at many levels, cell type-specific expression and function of its receptors remains poorly understood. Here we aimed to study 5-HT1-7 expression and function in CD1a- and CD1a+ human monocyte-derived DCs (moDCs). We found that the 5-HT2B receptor-subtype is solely expressed by the inflammatory CD1a+ moDC subset. Specific 5-HT2B activation potently inhibited TLR2, TLR3, and TLR7/8-induced proinflammatory cytokine and chemokine (TNF-?, IL-6, IL-8, IP-10, IL-12) but not type I interferon-? responses. 5-HT2B agonism also interfered with the polarization of CD1a+ moDC-primed CD4+ T cells towards inflammatory Th1 and Th17 effector lymphocytes. Here we report the subset-specific expression and immunomodulatory function of 5-HT2B in human moDCs. Our results expand the biological role of 5-HT2B which may act not only as a neurotransmitter receptor, but also as an important modulator of both innate and adaptive immune responses.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Scientific Reports. - 8 (2018), p. 1-12. -
További szerzők:Gogolák Péter (1968-) (biológus, immunológus) Koncz Gábor (1970-) (biológus, immunológus) Földvári Zsófia Pázmándi Kitti Linda (1984-) (molekuláris biológus, immunológus) Miltner Noémi (1990-) (molekuláris biológus) Póliska Szilárd (1978-) (biológus) Bácsi Attila (1967-) (immunológus) Djurovic, Srdjan Rajnavölgyi Éva (1950-) (immunológus)
Pályázati támogatás:GINOP-2.3.2-15-2016-00050
GINOP
PEOPLE-2013-COFUND
FP7
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001-es BibID:BIBFORM065529
Első szerző:Szabó Attila (molekuláris biológus, immunológus, filozófus)
Cím:The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells / Attila Szabo, Attila Kovacs, Jordi Riba, Srdjan Djurovic, Eva Rajnavolgyi, Ede Frecska
Dátum:2016
ISSN:1662-453X
Megjegyzések:N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper, we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, iPSCs), monocyte-derived macrophages (moMACs), and dendritic cells (moDCs). Results showed that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2) through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1) suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
DMT
dimethyltryptamine
hypoxia
sigma-1 receptor
cellular survival
cellular stress
ips-derived cortical neuron
monocyte-derived macrophage
MONOCYTE-DERIVED dendritic cell
Megjelenés:Frontiers in Neuroscience 10 (2016), p. 1-11. -
További szerzők:Kovács Attila István (1968-) (pszichiáter szakorvos) Riba, Jordi Djurovic, Srdjan Rajnavölgyi Éva (1950-) (immunológus) Frecska Ede (1953-) (pszichiáter)
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Intézményi repozitóriumban (DEA) tárolt változat
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