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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:	BIBFORM125809
Első szerző:	Ádám Dorottya (molekuláris biológus)
Cím:	The TRPM5 antagonist triphenylphosphine oxide increases sebaceous lipogenesis and modulates immune phenotype of human sebocytes in a TRPM5-independent manner / Ádám D., Arany J., Tóth K. F., Petö O., Nyitrai T., Tóth B. I., Póliska S., Zouboulis C. C., Oláh A.
Dátum:	2024
Megjegyzések:	It has recently been shown that transient receptor potential melastatin 5 (TRPM5) ion channels contributed to the maintenance of the anagen phase of the hair cycle. Because adjacent sebaceous glands also exhibited TRPM5 immunopositivity, topically applied TRPM5 modulators administered with the intention to influence hair growth may also affect sebaceous glands (SGs). Hence, we aimed to assess expression of TRPM5 as well as effects of 2 agonists and 1 antagonist (triphenylphosphine oxide [TPPO]) of TRPM5 on human SZ95 sebocytes. First, using complementary methods (RNA-Seq, RT-qPCR, western blot, siRNA-mediated gene silencing, fluorescent Na+- and Ca2+-measurements), we found that TRPM5 is not expressed in human sebocytes in a functionally active form.While non- cytotoxic (MTT-assay) concentrations of the activators were ineffective, TPPO promoted sebaceous lipogenesis (Nile Red). 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-2. Moreover, TPPO up-regulated interleukin (IL)-6 in an EGFR- and p38a MAPKdependent manner (RT-qPCR), while it decreased release of IL-8 (ELISA), and it down-regulated additional pro-inflammatory cytokines (chemokine (C-X-C motif) ligand [CXCL]-1, CXCL2, CXCL6, colony-stimulating factor 2, IL-32). Collectively, specific TRPM5 modulators are unlikely to exert direct SG-related side effects, while safe TPPO analogues may induce beneficial moderate lipogenic and anti-inflammatory effects in dry skin dermatoses.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idézhető absztrakt folyóiratcikk sebocyte acne TRPM5 TPPO
Megjelenés:	The Journal of Investigative Dermatology. - 144 : 12_Suppl (2024), p. S313. -
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)
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001-es BibID:	BIBFORM116425
Első szerző:	Arany József (klinikai laboratóriumi kutató, vegyész)
Cím:	Adenosine receptors are novel regulators of human sebocyte biology / Arany J., Ádám D., Cseszlai M., Nyitrai T., Zouboulis C. C., Oláh A.
Dátum:	2023
ISSN:	0022-202X 1523-1747
Megjegyzések:	We have previously shown that (-)-cannabidiol, a non-psychotropic phytocannabinoid, exerted complex anti-acne effects, some of which were found to be mediated by the A2A adenosine receptor. Thus, in the current study, we aimed to investigate the expression and functional role of adenosine receptors on human SZ95 sebocytes. First, besides confirming the expression of A2A receptor, we showed that A1 and A2B adenosine receptors were also expressed in human sebocytes (Q-PCR, western blot), whereas expression of A3 was found to be around detection limit (Q-PCR). Next, by using non-cytotoxic concentrations (MTT-assay) of selective modulators of A2A and A2B receptors, we found that administration of the A2B agonist BAY 60-6583 led to a small, but significant increase in the basal, homeostatic sebaceous lipogenesis, while the A2B antagonist alloxazine reduced the lipid synthesis (24- and 48-hour treatments; Nile Red). Interestingly, administration of ZM 241385 (an A2A antagonist that can also block A2B receptor at higher concentrations) resulted in a concentration-dependent decrease of the lipid synthesis in course of 24-hr treatments, but did not influence lipogenesis in case of longer (48-hr) experiments (Nile Red). Importantly, the A2A agonist CGS 21680 slightly, but significantly decreased basal sebaceous lipogenesis (24- and 48-hr treatments; Nile Red), and could also suppress the lipogenic effect of the "acne-mimicking" inflammatory lipid mediator arachidonic acid (48-hr treatments; Nile Red). Last, but not least, our preliminary data suggest that activation of A2A, but, intriguingly, not of A2B, receptor is efficient in suppressing the Toll-like receptor 4 activator lipopolysaccharide-induced pro-inflammatory response as well (Q-PCR). Taken together, our data indicate that several adenosine receptors are expressed on human sebocytes. These receptors differentially influence sebocyte biology, and activation of A2A receptor appears to exert promising anti-acne effects in our in vitro model systems.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idézhető absztrakt folyóiratcikk sebocyte acne adenosine receptor sebaceous lipogenesis
Megjelenés:	Journal Of Investigative Dermatology. - 143 : Suppl_11 (2023), p. S355. -
További szerzők:	Ádám Dorottya (1991-) (molekuláris biológus) Cseszlai M. Nyitrai Tamara (1999-) (molekuláris biológus) Zouboulis, Christos C. (1960-) (bőrgyógyász) Oláh Attila (1984-) (élettanász)
Pályázati támogatás:	EFOP-3.6.3-VEKOP-16-2017-00009 EFOP EFOP-3.6.1-16-2016-00022 EFOP János Bolyai Research Scholarship MTA 134235 OTKA ÚNKP-23-5-DE-477 Egyéb
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