Georgina Nagy

Publications of Georgina Nagy

• Altered peripheral invariant natural killer T cells in atopic dermatitis.

  Authors: Edit Gyimesi, Georgina Nagy, Éva Remenyik, Sándor Sipka, Margit Zeher, Tamás Bíró, Andrea Szegedi

  Journal of clinical immunology. 06/2011; 31(5):864-72.

  Conflicting data exist on the number of invariant NKT (iNKT) cells in atopic dermatitis (AD); furthermore, no data have been published on their functional capacity. The frequency and number ofConflicting data exist on the number of invariant NKT (iNKT) cells in atopic dermatitis (AD); furthermore, no data have been published on their functional capacity. The frequency and number of circulating CD3+6B11+ iNKT cells and their CD4+ and CD4- subpopulations were evaluated in peripheral blood obtained from 41 patients with AD by four-color flow cytometry. Likewise, functional properties of iNKT cells were measured by five-color intracellular cytokine staining. The number and percentage of total iNKT cells and their CD4/CD8 subpopulations were significantly lower than the controls. Of further importance, the CD4-CD8- (double negative, DN) iNKT subgroup showed the strongest positive correlation with total iNKT cells. In addition, the DN subgroup exhibited the most pronounced functional alteration with significantly decreased levels of intracellular IFNγ and significantly increased levels of intracellular IL-4 in AD patients compared with the controls. The significantly altered number and cytokine production of iNKT cells from AD patients suggests that these cells may play an important role in the pathogenesis of AD.

• Association between serum IL-16 levels and the degree of sensitization in patients with atopic dermatitis.

  Authors: Georgina Nagy, Krisztián Gáspár, Beatrix Irinyi, Mónika Gál, Judit Tumpek, Edit Gyimesi, Sándor Sipka, Éva Remenyik, Péter Szodoray, Andrea Szegedi

  International archives of allergy and immunology. 03/2011; 156(1):69-74.

  Interleukin (IL)-16 has been characterized as an immunomodulatory cytokine. Besides its chemotactic properties, IL-16 amplifies inflammatory processes and possesses immunoregulatory functions. OurInterleukin (IL)-16 has been characterized as an immunomodulatory cytokine. Besides its chemotactic properties, IL-16 amplifies inflammatory processes and possesses immunoregulatory functions. Our aim was to investigate the association between serum IL-16 levels and the degree of allergic sensitization in patients with atopic dermatitis (AD). The serum level of IL-16 was measured by immunoenzymatic assays. Eosinophil cell count, serum total and specific IgE levels were assessed; prick tests were also carried out. Based on specific IgE levels and prick tests, AD patients were divided into sensitized and nonsensitized subgroups, and correlations among serum IL-16, total IgE levels and eosinophil cell counts were measured in the total patient group and in subgroups. In the total patient group, significantly higher levels of IL-16 were found in the sera of patients with AD, compared to healthy individuals and patients with psoriasis. A significant correlation was detected between serum levels of IL-16 and total IgE, total IgE and eosinophil counts, but not between IL-16 and eosinophils. When sensitized and nonsensitized subgroups were compared, IL-16 levels showed a significant difference in subgroups that were divided based on specific IgE measurements, but not in those subgroups which were divided based on prick tests. On the other hand, serum total IgE levels showed a significant difference between sensitized and nonsensitized subgroups, assessed by the specific IgE method and also by prick test. Serum IL-16 levels of AD patients correlate to some extent with sensitization. This correlation is not as strong as the correlation between total IgE levels and allergic sensitization.

• PKCdelta is a positive regulator of chondrogenesis in chicken high density micromass cell cultures.

  Authors: Csaba Matta, Tamás Juhász, Zsolt Szíjgyártó, Bernadett Kolozsvári, Csilla Somogyi, Georgina Nagy, Pál Gergely, Róza Zákány

  Biochimie. 02/2011; 93(2):149-59.

  We aimed to elucidate the role of the Ca-independent PKC isoenzyme PKCdelta in the regulation of spontaneous in vitro chondrogenesis occurring in a 6-day-long culturing period in chicken limbWe aimed to elucidate the role of the Ca-independent PKC isoenzyme PKCdelta in the regulation of spontaneous in vitro chondrogenesis occurring in a 6-day-long culturing period in chicken limb bud-derived high density cell cultures (HDC). PKCdelta expression and activity were detectable throughout the entire culturing period with a peak on days 2 and 3, when most of the chondroblasts differentiate. To inhibit the activity of PKCdelta, either the natural compound rottlerin was transiently applied to the culture medium of HDC in 2.5, 5 or 10 μM concentrations, or gene silencing was performed by using PKCdelta shRNA. Rottlerin significantly reduced the overall PKC activity in enzyme activity assays of cell-free samples of untreated control HDC, probably via the inhibition of PKCdelta. On the contrary, we were unable to detect any consistent change of PKC enzyme activity assayed in samples of HDC treated with rottlerin during culturing. PKCdelta gene silencing resulted in a significantly lower PKC activity. Both rottlerin and PKCdelta shRNA caused a severe reduction in cartilage formation, furthermore protein and phospho-protein levels of Sox9, the key transcription factor of chondrogenesis, were also significantly decreased. Rottlerin lowered, while PKCdelta gene silencing elevated the phosphorylation status of ERK1/2. Our data suggest that PKCdelta stimulates chondrogenesis via influencing Sox9 and ERK1/2 phosphorylation, but the inhibition of cartilage formation in the rottlerin-treated HDC is probably PKCdelta independent and rottlerin might have different effects when applied to cells or to an in vitro enzyme activity assay.

• Inhibition of calcineurin by cyclosporine A exerts multiple effects on human melanoma cell lines HT168 and WM35.

  Authors: Tamás Juhász, Csaba Matta, Gábor Veress, Georgina Nagy, Zsolt Szíjgyártó, Zsanett Molnár, János Fodor, Róza Zákány, Pál Gergely

  International journal of oncology. 05/2009; 34(4):995-1003.

  The immunosuppressant cyclosporine A (CsA) is a specific pharmacological inhibitor of calcineurin, the Ca2+-calmodulin activated phospho-Ser/Thr-specific protein phosphatase. AlthoughThe immunosuppressant cyclosporine A (CsA) is a specific pharmacological inhibitor of calcineurin, the Ca2+-calmodulin activated phospho-Ser/Thr-specific protein phosphatase. Although calcineurin-inhibiting compounds are applied for local treatment of psoriasis or atopic dermatitis in dermatological practice, little is known about the functions of calcineurin in epidermis-derived malignancies. We investigated the effects of CsA on two human melanoma cell lines, the metastasis forming HT168 and WM35 established from an RGP primary lesion. CsA of 2 microM lowered the enzyme activity by 50% and caused elevation in both mRNA and protein expression of calcineurin. Cell proliferation was diminished, as well as the cellular morphology and the actin organization were altered in both cell lines. CsA increased cell death moderately in both cell lines and reduced the metabolic activity of HT168 cells, but not that of WM35 cells. CsA also elevated the expressions of both Bcl-2 and ERK1/2. Fibronectin guided migration of HT168 cells was stimulated under the effect of CsA, while that of WM35 cells was reduced, moreover, HT168 cells switched from the expression of beta3 to beta1 integrin, but WM35 cells continued to express beta3. Based on our results we propose a multiple, partly malignancy-dependent role of calcineurin in these melanoma cell lines.

• Immunological and Clinical Effects of Alphacalcidol in Patients with Psoriatic Arthropathy: Results of an Open, Follow-up Pilot Study.

  Authors: János Gaál, Gabriella Lakos, Péter Szodoray, Judit Kiss, Irén Horváth, Edit Horkay, Georgina Nagy, Andrea Szegedi

  Acta dermato-venereologica. 02/2009; 89(2):140-4.

  The aim of this study was to describe the effect of systemic alphacalcidol (1 OH vitamin D3) treatment on clinical and immunological parameters in patients with psoriatic arthropathy. Among the 19The aim of this study was to describe the effect of systemic alphacalcidol (1 OH vitamin D3) treatment on clinical and immunological parameters in patients with psoriatic arthropathy. Among the 19 patients investigated, 10 were treated with 0.25 microg oral alphacalcidol twice daily for 6 months, while 9 other patients served as controls. In the peripheral blood of the treated group but not in the controls, a statistically significant decrease was observed in the percentage of CD3/CD69-positive activated and CD8-positive interferon- -producing T cells and in the serum level of interferon- during the first 3 months and also in the clinical activity of the disease during the whole 6-month follow-up period. Our results show that systemic alphacalcidol treatment has an immunomodulatory effect on patients with psoriatic arthropathy. This effect is manifested by a short-term temporary decrease in type 1 immune responses and a continuous decrease in disease activity. Key words: alphacalcidol treatment; psoriatic arthropathy; immunomodulatory effect.

• Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling.

  Authors: Nóra Dobrosi, Balázs I Tóth, Georgina Nagy, Anikó Dózsa, Tamás Géczy, László Nagy, Christos C Zouboulis, Ralf Paus, László Kovács, Tamás Bíró

  The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 08/2008;

  We had previously shown that both locally produced endocannabinoids and exocannabinoids, via cannabinoid receptor-1 (CB1), are powerful inhibitors of human hair growth. To further investigate theWe had previously shown that both locally produced endocannabinoids and exocannabinoids, via cannabinoid receptor-1 (CB1), are powerful inhibitors of human hair growth. To further investigate the role of the cannabinoid system in pilosebaceous unit biology, we have explored in the current study whether and how endocannabinoids have an impact on human sebaceous gland biology, using human SZ95 sebocytes as cell culture model. Here, we provide the first evidence that SZ95 sebocytes express CB2 but not CB1. Also, prototypic endocannabinoids (arachidonoyl ethanolamide/anandamide, 2-arachidonoyl glycerol) are present in SZ95 sebocytes and dose-dependently induce lipid production and (chiefly apoptosis-driven) cell death. Endocannabinoids also up-regulate the expression of key genes involved in lipid synthesis (e.g., PPAR transcription factors and some of their target genes). These actions are selectively mediated by CB2-coupled signaling involving the MAPK pathway, as revealed by specific agonists/antagonists and by RNA interference. Because cells with "silenced" CB2 exhibited significantly suppressed basal lipid production, our results collectively suggest that human sebocytes utilize a paracrine-autocrine, endogenously active, CB2-mediated endocannabinoid signaling system for positively regulating lipid production and cell death. CB2 antagonists or agonists therefore deserve to be explored in the management of skin disorders characterized by sebaceous gland dysfunctions (e.g., acne vulgaris, seborrhea, dry skin).-Dobrosi, N., Tóth, B. I., Nagy, G., Dózsa, A., Géczy, T., Nagy, L., Zouboulis, C. C., Paus, R., Kovács, L., Bíró, T. Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling.

• Effect of natural phenol derivatives on skeletal type sarcoplasmic reticulum Ca2+ -ATPase and ryanodine receptor.

  Authors: Sándor Sárközi, János Almássy, Balázs Lukács, Nóra Dobrosi, Georgina Nagy, István Jóna

  Journal of muscle research and cell motility. 02/2007; 28(2-3):167-74.

  The effect of natural phenol derivatives was studied on skeletal type sarcoplasmic reticulum Ca(2+)-ATPase and ryanodine receptor. The majority of the tested derivatives exerted inhibitory effect onThe effect of natural phenol derivatives was studied on skeletal type sarcoplasmic reticulum Ca(2+)-ATPase and ryanodine receptor. The majority of the tested derivatives exerted inhibitory effect on the Ca(2+)-ATPase with an ascending sequence in regard to their effectiveness (IC(50)): cineole (3.33 mM) < ortho-vanillin (IC(50 )=1.13 mM) < 4-methyl-2-nitrophenol (1104 microM) < vanillin (525 microM) < thymol (224 microM) < carvacrol (162 microM). In two cases biphasic characteristic was observed: trans-anethole and meta-anisaldehyde first caused activation followed by inhibition (with IC(50)-s of 141 and 1903 microM respectively) as their concentration was increased. In some cases (cineole, ortho-vanillin, meta-anisaldehyde) total inhibition of Ca(2+)-ATPase could not be reached as the result of the limited solubility of these drugs. Para-anisaldehyde and 6-amino-meta-cresol did not show any effect up to 3 mM. In Ca(2+) release experiments drugs were applied on heavy sarcoplasmic reticulum vesicles isolated from skeletal muscle and actively loaded with calcium. Only thymol and carvacrol were able to evoke Ca(2+) release with EC(50) values of 158 +/- 16 and 211 +/- 55 microM respectively. Furthermore the effect of thymol and carvacrol was tested on the isolated ryanodine receptor incorporated into artificial lipid bilayer. Both drugs activated the RyR when applied in concentrations identical to their EC(50) values. These observations show that small differences in the structure of phenol derivatives sometimes have little impact on their effect on the sarcoplasmic reticulum Ca(2+)-ATPase or ryanodine receptor (thymol and carvacrol) whereas in certain cases they can completely abolish a particular effect (para- and meta-anisaldehyde).