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001-es BibID:	BIBFORM129513
035-os BibID:	(WoS)001482469000001 (Scopus)105004690504
Első szerző:	Ádám Dorottya (molekuláris biológus)
Cím:	The TRPM5 antagonist triphenylphosphine oxide (TPPO) increases sebaceous lipogenesis and modulates immune phenotype of human sebocytes in a TRPM5-independent manner / Ádám Dorottya, Arany József, Tóth Kinga Fanni, Pető Orsolya, Nyitrai Tamara, Tóth István Balázs, Póliska Szilárd, Christos C. Zouboulis, Oláh Attila
Dátum:	2025
ISSN:	0906-6705
Megjegyzések:	Transient receptor potential melastatin 5 (TRPM5) ion channel is expressed in human hair follicles, where its spontaneous activity contributes to the maintenance of the growing, anagen phase of the hair cycle. Because adjacent sebaceous glands also exhibited TRPM5 immunopositivity, topically applied TRPM5 modulators administered to influence hair growth may also affect sebaceous glands. Hence, we aimed to assess expression of TRPM5 as well as effects of TRPM5 modulators (activators: 2,5-dimethylpyrazine, 2-heptanone; antagonist: triphenylphosphine oxide [TPPO]) on human SZ95 sebocytes, i.e., on the best available in vitro model to study human sebaceous glands. First, using complementary methods (RNA-Seq, RT-qPCR, western blot, siRNA-mediated gene silencing, as well as fluorescent Na+- [SBFI AM] and Ca2+-measurements [Fura-2 AM]), we found that TRPM5 is not expressed in human sebocytes in a functionally active form. Importantly, while non-cytotoxic (MTT-assay) concentrations of the activators were ineffective, TPPO promoted sebaceous lipogenesis (Nile Red labeling). This effect was TRPM5-independent and was found to be mediated in an Akt- and epidermal growth factor receptor (EGFR)-dependent manner, most likely via the Akt-induced up-regulation of diacylglycerol O-acyltransferase (DGAT)-2. Moreover, TPPO up-regulated interleukin (IL)-6 in an EGFR- and p38? MAPK-dependent manner (RT-qPCR), while it decreased release of IL-8 (ELISA), and down-regulated additional pro-inflammatory cytokines (chemokine (C-X-C motif) ligand [CXCL]-1, CXCL2, CXCL6, colony-stimulating factor 2, IL-32; RNA-Seq). Collectively, specific TRPM5 modulators are unlikely to exert direct sebaceous gland-related side effects, while safe TPPO analogues may induce beneficial moderate lipogenic and anti-inflammatory effects in dry skin dermatoses.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk acne dry skin inflammation sebum sebocyte TPPO
Megjelenés:	Experimental Dermatology. - 34 : 5 (2025), p. 1-13. -
További szerzők:	Arany József (1990-) (klinikai laboratóriumi kutató, vegyész) Tóth Kinga Fanni (1992-) (molekuláris biológus, élettanász) Pető Orsolya Nyitrai Tamara (1999-) (molekuláris biológus) Tóth István Balázs (1978-) (élettanász) Póliska Szilárd (1978-) (biológus) Zouboulis, Christos C. (1960-) (bőrgyógyász) Oláh Attila (1984-) (élettanász)
Pályázati támogatás:	NKFIH 134235 Egyéb NKFIH 134725 Egyéb EFOP-3.6.3-VEKOP-16-2017-00009 EFOP EFOP-3.6.1-16-2016-00022 EFOP GINOP-2.3.2-15-2016-00050 GINOP BO/00660/21/5 MTA ÚNKP-22-5-DE-427 Egyéb ÚNKP-23-5-DE-477 Egyéb TKP2021-NKTA-34 Egyéb "Momentum" proof-of-concept fund (Faculty of Medicine, University of Debrecen) Egyéb
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001-es BibID:	BIBFORM060928
035-os BibID:	(WoS)000373072800283 (Scopus)84960114767
Első szerző:	Kovács Dóra (Biológus)
Cím:	Sebocytes differentially express and secrete adipokines / Dóra Kovács, Marianna Lovászi, Szilárd Póliska, Attila Oláh, Tamás Bíró, Imre Veres, Christos C. Zouboulis, Mona Ståhle, Ralph Rühl, Éva Remenyik, Dániel Törőcsik
Dátum:	2016
ISSN:	0906-6705
Megjegyzések:	In addition to producing sebum, sebocytes link lipid metabolism with inflammation at a cellular level and hence, greatly resemble adipocytes. However, so far no analysis was performed to identify and characterize the adipocyte-associated inflammatory proteins, the members of the adipokine family in sebocytes. Therefore, we determined the expression profile of adipokines (adiponectin, interleukin [IL] 6, resistin, leptin, serpin E1, visfatin, apelin, chemerin, retinol-binding protein 4 [RBP4] and monocyte chemoattractant protein 1 [MCP1]) in sebaceous glands of healthy and various disease-affected (acne, rosacea, melanoma and psoriasis) skin samples. Sebaceous glands in all examined samples expressed adiponectin, IL6, resistin, leptin, serpin E1 and visfatin, but not apelin, chemerin, RBP4 and MCP1. Confirming the presence of the detected adipokines in the human SZ95 sebaceous gland cell line we further characterized their expression and secretion patterns under different stimuli mimicking bacterial invasion (by using Toll-like receptor [TLR] 2 and 4 activators), or by 13-cis retinoic acid (13CRA; also known as isotretinoin), a key anti-acne agent. With the exception of resistin, the expression of all of the detected adipokines (adiponectin, IL6, leptin, serpin E1 and visfatin) could be further regulated at the level of gene expression, showing a close correlation with the secreted protein levels. Besides providing further evidence on similarities between adipocytes and sebocytes, our results strongly suggest that sebocytes are not simply targets of inflammation but may exhibit initiatory and modulatory roles in the inflammatory processes of the skin through the expression and secretion of adipokines.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Adipokine Inflammation Sebocyte
Megjelenés:	Experimental Dermatology. - 25 : 3 (2016), p. 194-199. -
További szerzők:	Lovászi Marianna (1986-) (biológus) Póliska Szilárd (1978-) (biológus) Oláh Attila (1984-) (élettanász) Bíró Tamás (1968-) (élettanász) Veres Imre (1963-) (bőrgyógyász) Zouboulis, Christos C. (1960-) (bőrgyógyász) Ståhle, Mona Rühl, Ralph (1969-) (vegyész) Remenyik Éva (1956-) (bőrgyógyász) Töröcsik Dániel (1979-) (bőrgyógyász)
Pályázati támogatás:	NN117020 OTKA TÁMOP-4.2.2.A-11/1/KONV-2012-0031 TÁMOP TÁMOP-4.2.4 A/2-11-1-2012-0001 TÁMOP FP7-PEOPLE-2013-IEF Egyéb "Lendület" LP2011-003/2015 Egyéb
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001-es BibID:	BIBFORM116512
035-os BibID:	(Scopus)85180437359 (WoS)001128766100001
Első szerző:	Tóth Kinga Fanni (molekuláris biológus, élettanász)
Cím:	Fluoxetine exerts anti-inflammatory effects on human epidermal keratinocytes and suppresses their endothelin release / Tóth Kinga Fanni, Ádám Dorottya, Arany József, Ramirez Yesid A., Bíró Tamás, Jennifer I. Drake, Alison O'Mahony, Szöllősi Attila Gábor, Póliska Szilárd, Ana Kilic, Michael Soeberdt, Christoph Abels, Oláh Attila
Dátum:	2024
ISSN:	0906-6705
Megjegyzések:	Fluoxetine is a safe antidepressant with remarkable anti-inflammatory actions; therefore, we aimed to investigate its effects on immortalized (HaCaT) as well as primary human epidermal keratinocytes in a polyinosinic-polycytidylic acid (p(I:C))-induced inflammatory model. We found that a non-cytotoxic concentration (MTT-assay, CyQUANT-assay) of fluoxetine significantly suppressed p(I:C)-induced expression and release of several pro-inflammatory cytokines (Q-PCR, cytokine array, ELISA), and it decreased the release of the itch mediator endothelins (ELISA). These effects were not mediated by the inhibition of the NF-?B or p38 MAPK pathways (western blot), or by the suppression of the p(I:C)-induced elevation of mitochondrial ROS production (MitoSOX Red labeling). Instead, unbiased activity profiling revealed that they were most likely mediated via the inhibition of the phosphoinositide 3-kinase (PI3K) pathway. Importantly, the PI3K-inhibitor GDC0941 fully mimicked the effects of fluoxetine (Q-PCR, ELISA). Although fluoxetine was able to occupy the binding site of GDC0941 (in silico molecular docking), and exerted direct inhibitory effect on PI3K (cell-free PI3K activity assay), it exhibited much lower potency and efficacy as compared to GDC0941. Finally, RNA-Seq analysis revealed that fluoxetine deeply influenced the transcriptional alterations induced by p(I:C)-treatment, and exerted an overall anti-inflammatory activity. Collectively, our findings demonstrate that fluoxetine exerts potent anti-inflammatory effects, and suppresses the release of the endogenous itch mediator endothelins in human keratinocytes, most likely via interfering with the PI3K pathway. Thus, clinical studies are encouraged to explore whether the currently reported beneficial effects translate in vivo following its topical administration in inflammatory and pruritic dermatoses.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk atopic dermatitis fluoxetine PI3K Toll-like receptor 3 inflammation keratinocyte itch endothelin
Megjelenés:	Experimental Dermatology. - 33 : 1 (2024), p. 1-15. -
További szerzők:	Ádám Dorottya (1991-) (molekuláris biológus) Arany József (1990-) (klinikai laboratóriumi kutató, vegyész) Ramirez, Yesid A. Bíró Tamás (1968-) (élettanász) Drake, Jennifer I. O'Mahony, Alison Szöllősi Attila Gábor (1982-) (élettanász) Póliska Szilárd (1978-) (biológus) Kilic, Ana Soeberdt, Michael Abels, Christoph Oláh Attila (1984-) (élettanász)
Pályázati támogatás:	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 NKFIH 125055 Egyéb NKFIH 134235 Egyéb NKFIH 134993 Egyéb János Bolyai Research Scholarship MTA ÚNKP-22-5-DE-427 Egyéb ÚNKP-23-5-DE-477 Egyéb TKP2021-NKTA-34 Egyéb Deutscher Akademischer Austauschdienst Egyéb Dr. August Wolff GmbH & Co. KG Arzneimittel Egyéb
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