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1.

001-es BibID:BIBFORM071072
035-os BibID:(WOS)000383091900301
Első szerző:Mihály Johanna (biológus, vegyész)
Cím:Establishment and optimization of pro-inflammatory model systems in human keratinocytes / Mihaly J., Angyal A., Szilagyi S. B., Tubak V., Soeberdt M., Abels C., Olah A., Biro T.
Dátum:2016
ISSN:0022-202X
Megjegyzések:Keratinocytes were already shown to express various pathogen-associated molecular pattern recognizing receptors, and to produce anti-microbial peptides and pro-inflammatory cytokines, which are important in regulating cutaneous immune processes. Thus, acting on keratinocytes augurs to be a highly efficient and targeted way to alleviate cutaneous inflammation. Therefore, in the current methodological study, we aimed to establish a wide array of easy-to-handle, keratinocyte-based pro-inflammatory model systems, in which efficiency of novel anti-inflammatory compounds can be investigated.The viability of immortalized (HaCaT, HPV-KER) human epidermal keratinocytes was investigated by MTT-assay. Pro-inflammatory response was assessed by measuring the expression (RT-qPCR) and release (ELISA) of selected pro-inflammatory cytokines upon various 3-, 6-, 12- and 24-hr treatments. The revealed optimal duration and dosing of the treatments together with the suggested cell types and read-out parameters are as follows 1. Non-specific irritation/inflammation model: 1 ?M SDS treatment for 24 hrs on HaCaT keratinocytes; recommended endpoint is IL8.2. Contact irritation/inflammation: 1 ?M NiCl2 treatment for 6 hrs on HPV-KERs; recommended read-outs are IL6 and IL8.3. Chemical irritation/inflammation: 300 ?M carvacrol (6 hrs; HPV-KER). Recommended endpoints: IL1?, TNF?, IL6 and IL8.4. Protease induced irritation/inflammation: 10 ?M SLIGRL treatment (3-6 hrs; HaCaT). Recommended endpoints: IL6 and IL8.5. UVB-induced inflammation: 40 mJ/cm2 treatments followed by 6-hr incubation on HPV-KERs; recommended read-outs are IL1?, IL1?, IL6, IL8 and TNF?.6. Poly-(I:C)-induced inflammation: 3-hr treatments on both HPV-KERs and HaCaT keratinocytes; recommended read-outs are IL1?, IL1?, Il6 and IL8.7. Atopic dermatitis-like irritation/inflammation: combined treatment with SEB (100 ng/ml) and TSLP (30 ng/ml) (48-72 hrs; HPV-KER). Read-out parameters: IL1?, TNF?, IL6 and IL8.We could successfully establish various different pro-inflammatory model systems suitable for multifaceted, medium throughput investigation of novel anti-inflammatory compounds.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
folyóiratcikk
anti-inflammatory, fluorinated phytocannabinoids
pro-inflammatory model systems
Megjelenés:Journal Of Investigative Dermatology. - 136 : 9 (2016), p. S212. -
További szerzők:Angyal Ágnes (1987-) (molekuláris biológus) Szilágyi S. B. Tubak Vilmos Soeberdt, Michael Abels, Christoph Oláh Attila (1984-) (élettanász) Bíró Tamás (1968-) (élettanász) (absztraktok)
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2.

001-es BibID:BIBFORM071070
035-os BibID:(WOS)000410115800448
Első szerző:Mihály Johanna (biológus, vegyész)
Cím:Assessment of the anti-inflammatory effects of fluorinated semi-synthetic phytocannabinoids in human in vitro inflammatory keratinocyte model systems / Mihaly J., Miltner N., Tubak V., Mechoulam R., Russo E., Biro T.
Dátum:2017
ISSN:0022-202X
Megjegyzések:It is common wisdom in pharmacology that fluorination can significantly increase the efficacy of the active components in pharmaceuticals ? actually, ca. 30% of the best-selling drugs worldwide contain fluorinated compounds. The laboratory of Prof. Mechoulam has recently synthesized a series of fluorinated derivatives of cannabidiol (CBD), the major non-psychoactive component of the plant Cannabis sativa. The goal of the current study was to assess the potential cutaneous anti-inflammatory actions of these compounds (F-CBDs).Effects of CBD and F-CBDs (HUF-101, HUF-103 and HU-559a) were investigated in seven, previously established in vitro human epidermal keratinocyte models (employing the immortalized HaCaT and HPV-KER keratinocyte cell lines) which mimic, as closely as possible, various human inflammatory skin conditions and diseases (e.g. microbial, UVB-induced, allergic, contact, and atopic dermatitis). Gene expression and protein release were assessed by RT-qPCR and ELISA, respectively. As expected, expressions of certain pro-inflammatory cytokines (e.g. interleukin [IL]-1?, IL-1?, IL-6 and IL-8) were significantly down-regulated upon the administration of CBD and F-CBDs in most models. Of great importance, however, all F-CBDs exhibited significantly higher efficacies in comparison to the non-fluorinated counterpart CBD, with the rank order of efficacy in the in vitro human epidermal keratinocyte models being HUF103 > HU559a > HU101.Our study provides the first evidence that F-CBDs exert remarkable anti-inflammatory actions on human epidermal keratinocytes. These intriguing data invite further pre-clinical and clinical studies to exploit the therapeutic potential of certain F-CBDs in a various cutaneous inflammatory conditions.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
folyóiratcikk
anti-inflammatory
fluorinated phytocannabinoids
Megjelenés:Journal Of Investigative Dermatology. - 137 : 10 (2017), p. S271. -
További szerzők:Miltner Noémi (1990-) (molekuláris biológus) Tubak Vilmos Mechoulam, Raphael Russo, Ethan Bíró Tamás (1968-) (élettanász) (absztraktok)
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3.

001-es BibID:BIBFORM071074
Első szerző:Mihály Johanna (biológus, vegyész)
Cím:Transient receptor potential vanilloid-3 regulates inflammatory actions of human epidermal keratinocytes / Mihaly J., Vasas N., Angyal A., Payer E., Kistamas K., Nanasi P., Szollosi A., Biro T.
Dátum:2015
ISSN:0022-202X
Megjegyzések:Several members of the vanilloid subfamily of transient receptor potential (TRPV) channels are expressed in the skin and play important roles in regulating cutaneous homeostasis. Our aim was to study the expression of TRPV3 ion channel and to investigate its role in normal human epidermal keratinocytes (NHEK).Carvacrol (CRV), a naturally occurring monoterpenoid TRPV3 agonist was administered on NHEKs. Cell viability and proliferation were determined by MTT- and CyQuant-assays, respectively. Gene expression and protein release were assessed by RT-qPCR, Western blot, indirect immuno labeling and ELISA, whereas functional activity of TRPV3 was investigated by whole-cell patch-clamp technique and Fluo-4 AM-based Ca2+-measurement. Selective gene silencing of TRPV3 was performed by RNAi.First, we confirmed that TRPV3 is indeed functionally active on NHEKs. Moreover, its activation by CRV decreased viability and proliferation of keratinocytes in a dose-dependent manner. Importantly, we could also show that expression of certain pro-inflammatory cytokines (interleukin [IL]-1?, IL-6, IL-8 and tumor necrosis factor-?) were upregulated upon CRV treatment in a TRPV3-dependent manner. Furthermore, we also found that silencing of TRPV3 expression was able to efficiently abrogate the aforementioned pro-inflammatory response as well as CRV-induced release of IL-6 and IL-8.Our results strongly argue for that TRPV3 plays a pivotal role in regulating inflammatory actions of epidermal keratinocytes. Antagonizing its activity could therefore be a promising novel therapeutic tool in the management of certain cutaneous inflammatory diseases e.g. in atopic dermatitis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
TRPV3
pro-inflammatory model systems
Megjelenés:Journal of Investigative Dermatology 135 : Suppl. 2 (2015), p. S44. -
További szerzők:Molnárné Vasas Nikolett (1987-) (élettanász) Angyal Adrienn Páyer Edit (1982-) Kistamás Kornél (1986-) (biológus) Nánási Péter Pál (1956-) (élettanász) Szöllősi Attila Gábor (1982-) (élettanász) Bíró Tamás (1968-) (élettanász) (absztraktok)
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4.

001-es BibID:BIBFORM074173
035-os BibID:(WOS)000431498600282
Első szerző:Miltner Noémi (molekuláris biológus)
Cím:Assessment of the anti-inflammatory effects of cannabidiol and its fluorinated derivative in in vitro and in vivo models of atopic dermatitis / Miltner Noémi, Béke Gabriella, Angyal Ágnes, Kemény Ágnes, Pintér Erika, Helyes Zsuzsanna, Bíró Tamás, Mihály Johanna
Dátum:2018
ISSN:0022-202X 1523-1747
Megjegyzések:Noémi Miltner1, Gabriella Béke1, Ágnes Angyal1, Ágnes Kemény2, Erika Pintér2, Zsuzsanna Helyes2, Tamás Bíró1,3, Johanna Mihály1Assessment of the anti-inflammatory effects of cannabidiol and its fluorinated derivative in in vitro and in vivo models of atopic dermatitis1Department of Immunology, Faculty of Medicine, University of Debrecen, Hungary2Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, Hungary3Phytecs Inc., Los Angeles, CA, USAIt is common wisdom in pharmacology that fluorination can significantly increase the efficacy of the active components in pharmaceuticals ? actually, ca. 30% of the best-selling drugs worldwide contain fluorinated compounds. The aim of the current study was to assess the potential anti-inflammatory effects of cannabidiol (CBD), the major non-psychoactive component of the pant Cannabis sativa, and its fluorinated derivative (HUF-101) in various experimental systems modeling atopic dermatitis (AD). For the in vitro AD model, human epidermal keratinocytes were challenged with the combination of Staphylococcus aureus enterotoxin B (SEB) and thymic stromal lymphopoietin (TSLP), and expressions of certain marker molecules were assessed by RT-qPCR and ELISA. For the in vivo model, mice were sensitized with 2% oxazolone (OXA) before elicitation. Test compounds were applied topically (1 and 10 ?M) after inducing skin inflammation and edema formation (in the ears) was measured with an engineer's micrometer.In the in vitro model, expressions of certain pro-inflammatory cytokines (e.g. interleukin [IL]-1?, IL-1?, IL-6 and IL-8) were significantly down-regulated upon the administration of CBD and HUF-101. Of great importance, however, HUF-101 exhibited significantly higher potency in comparison to CBD. In the in vivo model, topical application of 1 ?M CBD significantly reduced the OXA-induced ear edema; however, 10 ?M CBD exerted insignificant effect. In contrast, HUF-101 attenuated OXA-induced edema formation at both concentrations. Intriguingly, similar to the in vitro conditions, the anti-inflammatory potency of HUF-101 was significantly greater than that of CBD. Our study provides the first evidence that CBD and its fluorinated derivative exert significant anti-inflammatory actions in models of AD. These intriguing data invite further pre-clinical and clinical studies to exploit the therapeutic potential of certain CBD derivatives in cutaneous inflammatory conditions.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
folyóiratcikk
Megjelenés:Journal of Investigative Dermatology. - 138 : 5S (2018), p. S173. -
További szerzők:Béke Gabriella (1987-) (molekuláris biológus) Angyal Ágnes (1987-) (molekuláris biológus) Kemény Ágnes Pintér Erika Helyes Zsuzsanna Bíró Tamás (1968-) (élettanász) (absztraktok) Mihály Johanna (1982-) (biológus, vegyész)
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5.

001-es BibID:BIBFORM071182
Első szerző:Szabó Imre Lőrinc (általános orvos)
Cím:Transient Receptor Potential Vanilloid-4 Inhibits Human Hair Growth / I. L. Szabó, E. Herczeg-Lisztes, J. Mihály, A. Oláh, T. Bíró
Dátum:2015
ISSN:0022-202X
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
Megjelenés:Journal Of Investigative Dermatology. - 135 : Suppl. 2. (2015), p. S65. -
További szerzők:Lisztes Erika (1986-) (élettanász) Mihály Johanna (1982-) (biológus, vegyész) Oláh Attila (1984-) (élettanász) Bíró Tamás (1968-) (élettanász) (absztraktok)
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