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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: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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3.

001-es BibID:BIBFORM071068
035-os BibID:(WOS)000423029700020 (Scopus)85041655428
Első szerző:Szöllősi Attila Gábor (élettanász)
Cím:Activation of TRPV3 Regulates Inflammatory Actions of Human Epidermal Keratinocytes / Szöllősi A. G., Vasas N., Angyal Á., Kistamás K., Nánási P. P., Mihály J., Béke G., Herczeg-Lisztes E., Szegedi A., Kawada N., Yanagida T., Mori T., Kemény L., Bíró T.
Dátum:2018
Megjegyzések:Transient receptor potential (TRP) ion channels were first characterized on neurons, where they are classically implicated in sensory functions; however, research in recent decades has shown that many of these channels are also expressed on non-neuronal cell types. Emerging findings have highlighted the role of TRP channels in the skin, where they have been shown to be important in numerous cutaneous functions. Of particular interest is TRPV3, which was first described on keratinocytes. Its functional importance was supported when its gain-of-function mutation was linked to Olmsted syndrome, which is characterized by palmoplantar keratoderma, periorifacial hyperkeratosis, diffuse hypotrichosis and alopecia, as well as itch. In spite of these exciting results, we have no information about the role and functionality of TRPV3 on keratinocytes at the cellular level. In our current study, we have identified TRPV3 expression both on human skin and cultured epidermal keratinocytes. TRPV3 stimulation was found to function as a Ca2+-permeable ion channel which suppresses proliferation of epidermal keratinocytes and induces cell death. Stimulation of the channel also triggers a strong proinflammatory response via the NF-?B pathway. Collectively our data shows that TRPV3 is functionally expressed on human epidermal keratinocytes and that it plays a role in cutaneous inflammatory processes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
inflammation
keratinocyte
nuclear factor kappa-light-chain-enhancer of activated B cells
transient receptor potential vanilloid
Megjelenés:Journal of Investigative Dermatology. - 138 : 2 (2018), p. 365-374. -
További szerzők:Molnárné Vasas Nikolett (1987-) (élettanász) Angyal Ágnes (1987-) (molekuláris biológus) Kistamás Kornél (1986-) (biológus) Nánási Péter Pál (1956-) (élettanász) Mihály Johanna (1982-) (biológus, vegyész) Béke Gabriella (1987-) (molekuláris biológus) Lisztes Erika (1986-) (élettanász) Szegedi Andrea (1964-) (bőrgyógyász) Kawada, Naoki Yanagida, Takashi Mori, Tomohiro Kemény Lajos Bíró Tamás (1968-) (élettanász)
Pályázati támogatás:OTKA 105369
OTKA
NKFIH K120552
Egyéb
NKFIH K120187
Egyéb
GINOP-2.3.2-15-2016-00015
GINOP
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DOI
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