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001-es BibID:	BIBFORM048926
035-os BibID:	PMID:24227782
Első szerző:	Chimote, Ameet A.
Cím:	Selective Inhibition of KCa3.1 Channels Mediates Adenosine Regulation of the Motility of Human T Cells / Ameet A. Chimote, Peter Hajdu, Vladimir Kucher, Nina Boiko, Zerrin Kuras, Orsolya Szilagyi, Yeo-Heung Yun, Laura Conforti
Dátum:	2013
ISSN:	0022-1767 1550-6606
Megjegyzések:	Adenosine, a purine nucleoside, is present at high concentrations in tumors, where it contributes to the failure of immune cells to eliminate cancer cells. The mechanisms responsible for the immunosuppressive properties of adenosine are not fully understood. We tested the hypothesis that adenosine's immunosuppressive functions in human T lymphocytes are in part mediated via modulation of ion channels. The activity of T lymphocytes relies on ion channels. KCa3.1 and Kv1.3 channels control cytokine release and, together with TRPM7, regulate T cell motility. Adenosine selectively inhibited KCa3.1, but not Kv1.3 and TRPM7, in activated human T cells. This effect of adenosine was mainly mediated by A2A receptors, as KCa3.1 inhibition was reversed by SCH58261 (selective A2A receptor antagonist), but not by MRS1754 (A2B receptor antagonist), and it was mimicked by the A2A receptor agonist CGS21680. Furthermore, it was mediated by the cAMP/protein kinase A isoform (PKAI) signaling pathway, as adenylyl-cyclase and PKAI inhibition prevented adenosine effect on KCa3.1. The functional implication of the effect of adenosine on KCa3.1 was determined by measuring T cell motility on ICAM-1 surfaces. Adenosine and CGS21680 inhibited T cell migration. Comparable effects were obtained by KCa3.1 blockade with TRAM-34. Furthermore, the effect of adenosine on cell migration was abolished by pre-exposure to TRAM-34. Additionally, adenosine suppresses IL-2 secretion via KCa3.1 inhibition. Our data indicate that adenosine inhibits KCa3.1 in human T cells via A2A receptor and PKAI, thereby resulting in decreased T cell motility and cytokine release. This mechanism is likely to contribute to decreased immune surveillance in solid tumors.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Journal of Immunology. - 191 : 12 (2013), p. 6273-6280. -
További szerzők:	Hajdu Péter (1975-) (biofizikus) Kucher, Vladimir Boiko, Nina Kuras, Zerrin Szilágyi Orsolya (1985-) (molekuláris biológus, biokémikus) Yun, YeoHeung Conforti, Laura
Pályázati támogatás:	TÁMOP-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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001-es BibID:	BIBFORM020764
Első szerző:	Kis-Tóth Katalin (immunológus)
Cím:	Voltage-Gated Sodium Channel Nav1.7 Maintains the Membrane Potential and Regulates the Activation and Chemokine-Induced Migration of a Monocyte-Derived Dendritic Cell Subset / Katalin Kis-Toth, Peter Hajdu, Ildiko Bacskai, Orsolya Szilagyi, Ferenc Papp, Attila Szanto, Edit Posta, Peter Gogolak, Gyorgy Panyi, Eva Rajnavolgyi
Dátum:	2011
Megjegyzések:	Expression of CD1a protein defines a human dendritic cell (DC) subset with unique functional activities. We aimed to study the expression of the Nav1.7 sodium channel and the functional consequences of its activity in CD1a(-) and CD1a(+) DC. Single-cell electrophysiology (patch-clamp) and quantitative PCR experiments performed on sorted CD1a(-) and CD1a(+) immature DC (IDC) showed that the frequency of cells expressing Na(+) current, current density, and the relative expression of the SCN9A gene encoding Nav1.7 were significantly higher in CD1a(+) cells than in their CD1a(-) counterparts. The activity of Nav1.7 results in a depolarized resting membrane potential (-8.7 +/- 1.5 mV) in CD1a(+) IDC as compared with CD1a(-) cells lacking Nav1.7 (-47 +/- 6.2 mV). Stimulation of DC by inflammatory signals or by increased intracellular Ca(2+) levels resulted in reduced Nav1.7 expression. Silencing of the SCN9A gene shifted the membrane potential to a hyperpolarizing direction in CD1a(+) IDC, resulting in decreased cell migration, whereas pharmacological inhibition of Nav1.7 by tetrodotoxin sensitized the cells for activation signals. Fine-tuning of IDC functions by a voltage-gated sodium channel emerges as a new regulatory mechanism modulating the migration and cytokine responses of these DC subsets
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban ACTIVATION article Cells Electrophysiology Human Hungary immunology Sodium Tetrodotoxin
Megjelenés:	The Journal of Immunology. - 187 : 3 (2011), p. 1273-1280. -
További szerzők:	Hajdu Péter (1975-) (biofizikus) Bacskai Ildikó (1985-) (immunológus) Szilágyi Orsolya (1985-) (molekuláris biológus, biokémikus) Papp Ferenc (1979-) (biofizikus) Szántó Attila (1976-) (orvos, biokémikus) Feketéné Posta Edit (1986-) (reumatológus) Gogolák Péter (1968-) (biológus, immunológus) Panyi György (1966-) (biofizikus) Rajnavölgyi Éva (1950-) (immunológus)
Pályázati támogatás:	TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP Molekuláris immunológia TÁMOP-4.2.2-08/1-2008-0015 TÁMOP
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat Szerző által megadott URL
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