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001-es BibID:	BIBFORM106381
035-os BibID:	(PMID)36502939 (WoS)000984536200001 (Scopus)85149686723
Első szerző:	Alimohammadi, Shahrzad (Gyógyszerész)
Cím:	TRPV4 activation increases the expression of CD207 (Langerin) of monocyte-derived Langerhans cells, without affecting their maturation / Alimohammadi Shahrzad, Pénzes Zsófia, Horváth Dorottya, Gyetvai Ágnes, Bácsi Attila, Kis Nikoletta Gréta, Németh Ákos, Arany József, Oláh Attila, Lisztes Erika, Tóth Balázs István, Bíró Tamás, Szöllősi Attila Gábor
Dátum:	2023
ISSN:	0022-202X 1523-1747
Megjegyzések:	Langerhans cells (LCs) are the sole professional antigen-presenting cell normally found in the human epidermal compartment. Research into their physiological role is hindered by the fact that they are invariably activated during isolation from the skin. To overcome this challenge, we turned to a monocyte-derived LC model (moLC), which we characterized with RNASeq, and compared the transcriptome of moLCs to donor-matched immature dendritic cells. We found that moLCs express markers characteristic of LC2 cells, as well as transient receptor potential vanilloid 4 (TRPV4). TRPV4 is especially important in skin, as it has been linked to conservation of the skin barrier, immunological responses as well as acute and chronic itch, but we know little about its function on LCs. Our results show that TRPV4 activation increased the expression of Langerin and led to increased intracellular calcium concentration in moLCs. Regarding the functionality of moLCs, we found that TRPV4 agonism had a mitigating effect on their inflammatory responses, since it decreased their cytokine production, and T cell activating capability. As TRPV4 has emerged as a potential therapeutic target in dermatological conditions, it is important to highlight LCs as a novel target of these therapies.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Langerhans sejt Dendritikus sejt Immunológia Természetes immunitás
Megjelenés:	Journal Of Investigative Dermatology. - 143 : 5 (2023), p. 801-811.e10. -
További szerzők:	Pénzes Zsófia (1992-) (klinikai laboratóriumi kutató) Horváth Dorottya (1994-) (molekuláris biológus) Gyetvai Ágnes Bácsi Attila (1967-) (immunológus) Kis Gréta (1979-) (környezetkutató) Németh Ákos (1984-) (gyógyszer-vegyészmérnök, közgazdász) Arany József (1990-) (klinikai laboratóriumi kutató, vegyész) Oláh Attila (1984-) (élettanász) Lisztes Erika (1986-) (élettanász) Tóth István Balázs (1978-) (élettanász) Bíró Tamás (1968-) (élettanász) Szöllősi Attila Gábor (1982-) (élettanász)
Pályázati támogatás:	125053 OTKA 128034 OTKA 134235 OTKA GINOP-2.3.2-15-2016-00015 GINOP GINOP-2.3.3-15-2016-00020 GINOP EFOP-3.6.3-VEKOP-16-2017-00009 EFOP MTA-DE MTA
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001-es BibID:	BIBFORM118923
035-os BibID:	(cikkazonosító)176399 (WoS)001186776000001 (Scopus)85185499906
Első szerző:	Pázmándi Kitti Linda (molekuláris biológus, immunológus)
Cím:	Ginger-derived bioactive compounds attenuate the Toll-like receptor mediated responses of human dendritic cells / Kitti Pázmándi, Beatrix Ágics, Attila Gábor Szöllősi, Attila Bácsi, Tünde Fekete
Dátum:	2024
ISSN:	0014-2999
Megjegyzések:	Ginger has been used for thousands of years for the treatment of many illnesses, from nausea to migraines. Recently, an interest has grown in ginger compounds in the context of autoimmune and inflammatory diseases due to their significant anti-inflammatory effects. Nevertheless, the effects and mechanism of action of these phytochemicals in human immune cells, particularly in dendritic cells (DCs) are unclear. In the present study, we investigated the effects of 6-gingerol and 6-shogaol, the major compounds found in ginger rhizome, on the functionality of primary human monocyte-derived DCs (moDCs). Here we report for the first time that 6-gingerol and 6-shogaol dampen the immunogenicity of human DCs by inhibiting their activation, cytokine production and T cell stimulatory ability. In particular, the bioactive compounds of ginger dose-dependently inhibited the upregulation of activation markers, and the production of different cytokines in response to synthetic Toll-like receptor (TLR) ligands. Moreover, both compounds could significantly reduce the Escherichia coli-triggered cytokine production and T cell stimulatory capacity of moDCs. We also provide evidence that the ginger-derived compounds attenuate DC functionality via inhibiting the nuclear factor-?B (NF-kB), mitogen activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) signaling cascades. Further, 6-shogaol but not 6-gingerol activates the AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (NRF2) pathways that might contribute to its anti-inflammatory action. Altogether, our results indicate that ginger-derived phytochemicals exert their anti-inflammatory activities via multiple mechanisms and suggest that 6-shogaol is more potent in its ability to suppress DC functionality than 6-gingerol.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Dendritic cell TLR signaling anti-inflammatory cytokine gingerol shogaol
Megjelenés:	European Journal Of Pharmacology. - 967 (2024), p. 1-16. -
További szerzők:	Ágics Beatrix (1995-) Szöllősi Attila Gábor (1982-) (élettanász) Bácsi Attila (1967-) (immunológus) Fekete Tünde (1984-) (immunológus, molekuláris biológus, mikrobiológus)
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001-es BibID:	BIBFORM114466
035-os BibID:	(Scopus)85169695767 (cikkazonosító)1240800 (WOS)001058511200001
Első szerző:	Pénzes Zsófia (klinikai laboratóriumi kutató)
Cím:	The dual role of cannabidiol on monocyte-derived dendritic cell differentiation and maturation / Zsófia Pénzes, Shahrzad Alimohammadi, Dorottya Horváth, Attila Oláh, Balázs István Tóth, Attila Bácsi, Attila Gábor Szöllősi
Dátum:	2023
ISSN:	1664-3224
Megjegyzések:	Introduction: Extracts and compounds isolated from hemp (Cannabis sativa) are increasingly gaining popularity in the treatment of a number of diseases, with topical formulations for dermatological conditions leading the way. Phytocannabinoids such as ( )-cannabidiol, ( )-cannabinol and ( )-?9-tetrahydrocannabivarin (CBD, CBN, and THCV, respectively), are present in variable amounts in the plant, and have been shown to have mostly anti-inflammatory effects both in vitro and in vivo, albeit dominantly in murine models. The role of phytocannabinoids in regulating responses of dendritic cells (DCs) remains unclear. Methods: Our research aimed to investigate the effects of CBD, CBN, and THCV on human DCs differentiated from monocytes (moDCs). moDCs were treated with up to 10 ?M of each phytocannabinoid, and their effects on viability, differentiation, and maturation were assessed both alone, and in conjunction with TLR agonists. The effects of CBD on cytokine production, T cell activation and polarization as well as the transcriptome of moDCs was also determined. Results: Phytocannabinoids did not influence the viability of moDCs up to 10 ?M, and only CBD had effects on maturational markers of moDCs, and neither compound influenced LPS-induced activation at 10 ?M. Since only CBD had measurable effects on moDCs, in our subsequent experiments we tested the effect only of that pCB. On moDCs differentiated in the presence of CBD subsequent activation by LPS induced a markedly different, much more tolerogenic response. CBD-treated moDCs also produced significantly more interleukin (IL)-6, TNF? and, importantly, IL-10 in response to LPS, which shows a shift toward anti-inflammatory signaling, as well as a more robust secretory response in general. To rule out the possibility that these effects of CBD are specific to TLR4 signaling, we determined the effect of CBD on TLR7/8-induced maturation as well, and saw similar, although less marked responses. CBD-treated moDCs were also less efficient at activating naïve T cells after LPS stimulation, further supporting the tolerogenic effect of this phytocannabinoid on moDCs. Reactome pathway analysis showed an inflammatory response to LPS in moDCs, and to a lesser extent to CBD as well. In contrast CBD-treated moDCs responded to LPS with a shift towards a more tolerogenic phenotype, as IL-10 signaling was the most prominently induced pathway in this group. Discussion: Our results show that CBD achieves an anti-inflammatory effect on adaptive immune responses only in the presence of an activating stimuli on moDCs by reprogramming cells during long-term treatment, and not through acute, short-term effects.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk fitokannabinoidok kannabidiol monocita-eredetű dendritikus sejtek veleszületett immunitás T sejt proliferáció
Megjelenés:	Frontiers in Immunology. - 14 (2023), p. 1240800. -
További szerzők:	Alimohammadi, Shahrzad (1991-) (Gyógyszerész) Horváth Dorottya (1994-) (molekuláris biológus) Oláh Attila (1984-) (élettanász) Tóth István Balázs (1978-) (élettanász) Bácsi Attila (1967-) (immunológus) Szöllősi Attila Gábor (1982-) (élettanász)
Pályázati támogatás:	128034 OTKA 134993 OTKA 134235 OTKA 134725 OTKA GINOP-2.3.2-15-2016-00026 GINOP GINOP-2.3.3-15-2016-00020 GINOP EFOP-3.6.3-VEKOP-16-2017-00009 EFOP
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