Quantitative analysis of transforming growth factor beta isoforms mRNA TGF-β1-3 in the patients with psoriasis

Michalska-Bańkowska, Anna; Wcisło‐Dziadecka, Dominika; Grabarek, Beniamin Oskar; Mazurek, Urszula; Brzeźińska-Wcisło, Ligia; Salwowska, Natalia; Michalski, Piotr

doi:10.25121/pnm.2018.31.1a.4

Cited by 3 publications

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“…There were several reasons for us to study the microarray gene expression profile associated with the signaling pathways induced by TGF β . Firstly, in our previous studies, we observed that under the influence of cyclosporin A therapy in patients with psoriasis, there is a change in the transcriptional activity of TGFβ1-3 and TGFβRI-III [ 17 , 18 ]. Studies have indicated that CsA therapy significantly increases the risk of skin cancer [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…Depending on the biological context, including changes in the level of secretion of interleukins (IL), IL-1, IL-6, and IL-8, TGF β may inhibit or promote the proliferation of keratinocytes [ 13 , 14 ]. Despite observations [ 15 , 16 ], including ours [ 17 , 18 ], that TGF β may become a complementary molecular marker in the diagnosis of the severity of the psoriatic process [ 15 – 18 ], the exact mechanism of its action is still not fully understood.…”

Section: Introductionmentioning

confidence: 94%

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The Influence of Adalimumab and Cyclosporine A on the Expression Profile of the Genes Related to TGFβ Signaling Pathways in Keratinocyte Cells Treated with Lipopolysaccharide A

Adwent

Grabarek

Kojs‐Mrożkiewicz³

et al. 2020

Mediators of Inflammation

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Background. In the treatment of moderate to severe psoriasis, cyclosporine A (CsA) conventional therapy is used and biological, anti-cytokine treatment using, for example, anti-TNF drug—adalimumab. Aim. This study aimed at investigating the effect of CsA and adalimumab on the profile of mRNAs and protein expression associated with transforming growth factor β (TGFβ) pathways in human keratinocyte (HaCaT) culture previously exposed to lipopolysaccharide (LPS). Materials and Methods. HaCaT culture was exposed to 1 ng/ml LPS for 8 hours+8 μg/ml adalimumab for 2, 8, and 24 hours or 1 ng/ml LPS for 8 hours+100 ng/ml CsA for 2, 8, and 24 hours and compared to the control culture. Sulphorodamine B cytotoxicity assay was performed. The expression profile of mRNA related to TGFβ paths was indicated by microarray and RTqPCR analyses. The ELISA test was used to analyze changes on the proteome level. Statistical analysis consisted of ANOVA analysis and the post hoc Tukey test (p<0.05). Results. The cytotoxicity test showed that LPS, adalimumab, and cyclosporine in the concentration used in this experiment did not have any cytotoxicity effect on HaCaT cells. The largest fold changes (FC) in expression in (∣FC∣>4.00) was determined for TGFβ1-3, TGFβRI-III, SKIL, SMURF2, SMAD3, BMP2, BMP6, JAK2, UBE2D1, SKP2, EDN1, and PRKAR2B (p<0.05). In addition, on the protein level, the direct changes observed at mRNA were the same. Conclusion. Analysis of the microarray expression profile of genes associated with TGFβ signaling pathways has demonstrated the potential of cyclosporin A and adalimumab to induce changes in their transcriptional activity. The anti-TNF drug seems to affect TGFβ cascades to a greater extent than cyclosporin A. The obtained results suggest that the regularity of taking the drug is important for the efficacy of psoriasis therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

The Influence of Adalimumab and Cyclosporine A on the Expression Profile of the Genes Related to TGFβ Signaling Pathways in Keratinocyte Cells Treated with Lipopolysaccharide A

Adwent

Grabarek

Kojs‐Mrożkiewicz³

et al. 2020

Mediators of Inflammation

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“…The inclusion and exclusion criteria were described in our previous work (Michalska-Ba nkowska et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

The impact of diabetes and metabolic syndromes to the effectiveness of cyclosporine a pharmacotherapy in psoriatic patients

Michalska-Bańkowska

Grabarek

Wcisło‐Dziadecka

et al. 2019

Dermatologic Therapy

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Metabolic diseases concurrent with psoriasis may considerably affect the intensity of its symptoms and therapy efficacy. Cyclosporine A (CsA) is one of the medicines used in conventional therapy of psoriasis. The aim of the study was to determine whether Diabetes 2 and metabolic syndromes influence the efficacy of the CsA therapy in psoriatic patients. The sample group was composed of 32 patients with diagnosed moderate to severe forms of psoriasis vulgaris. The group was divided into subgroups, with regard to concurrently occurring Diabetes 2 and metabolic syndromes. The subgroups were composed of as follows: with diabetes—7 patients, without diabetes—25, with metabolic syndrome—15, without concurrent metabolic syndrome—17, with a metabolic syndrome without diabetes—8 and with both a metabolic syndrome and diabetes—7 patients. The efficacy of therapy was evaluated in each subgroup on the basis of the following scales: PASI, BSA, DLQI on the day of therapy commencing, after 42 and 84 days of the CsA therapy. The statistical analysis was performed with the use of STATISICA 12 (Cracow, Poland; p < .05). The following tests were used: The ANOVA Friedeman test, the posthoc test for ANOVA Friedeman test, the Mann–Whitney U test. We observed clinical improvement measured with PASI BSA scales in each subgroup. The patients themselves also reported improved comfort in their lives, which is confirmed by the lower score in the DLQI scale after 42 and 84 days of the pharmacotherapy. Differences in the values of each scale in a given subgroup turned to be statistically significant. The biggest differences occur after the first 42 days of therapy and they last in the later period of observations. We did not determine any statistically significant differences as a response to treatment in the subgroups subject to comparison. Diabetes and a metabolic syndrome concurrent with psoriasis vulgaris do not affect the efficacy of CsA therapy, which indicates no necessity to modify the standard dosage of the medicine and therapy regime.

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“…The aim of the paper is to analyse regularities between significant factors in psoriasis and signalling pathways activated by them [14][15][16][17][18][19]. Furthermore, the role of epigenetic mechanism of gene expression regulation by miRNA, which could constitute an independent marker system in diagnostics and assessment of treatment efficacy, will be discussed [16,19].…”

Section: And Therapeutic Algorithmsmentioning

confidence: 99%

“…Poprzednie nasze prace dotyczyły roli cytokin TNF [15], IL-12/23 [16], IL-17 [17], TGF-β [14,18], układu histaminergicznego [19] oraz roli cząsteczek mikroRNA (miRNA) w patogenezie chorób o podłożu zapalnym [16,19]. Oprócz analizy pojedynczej ścieżki sygnałowej ważnym zagadnieniem jest poszukiwanie wzajemnych zależności między kaskadami sygnalizacyjnymi aktywowanymi przez poszczególne cytokiny i poznanie mechanizmów regulacji ekspresji ich genów [22].…”

Section: And Therapeutic Algorithmsunclassified

Signaling pathways associated with interleukins 12 and 23 and epigenetic mechanism of sequential-specific regulation of expression of related genes by miRNAs as molecular markers for assessing the potential of anti-cytokine therapies

Grabarek¹,

Wcisło‐Dziadecka²,

Mazurek³

2019

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The molecular targeted therapy is focused on blocking the activity of specific cytokines and the signalling cascades they activate. In the treatment of psoriasis, this type of therapy is based on treatment with anti-tumor necrosis factor drugs, anti-IL-12/23, anti-IL-17, inhibitors of JAK kinases. Interleukins 12 and 23 interact with the receptors to trigger the JAK/STAT signalling pathway, the end products of which are other cytokines, e.g. tumour necrosis factor, IL-17, interferon g. These cytokines affect both IL-12/23 shaping their concentration profile, as well as trigger other signalling paths themselves. Gene expression is regulated by DNA methylation, miRNA molecules and histone protein modifications. The miRNA seems to be a promising model of a molecular marker system. Understanding the interrelationships between individual signalling pathways associated with IL-12 and IL-23 and the role of epigenetic mechanisms to regulate their expression is important for the development and implementation of new diagnostic-therapeutic schemes and the further development of personalized medicine. streszczenie Terapia ukierunkowana molekularnie skoncentrowana jest na blokowaniu aktywności określonych cytokin i aktywowanych przez nie kaskad sygnałowych. W łuszczycy opiera się ona na leczeniu wieloma grupami leków (leki anty-TNF, anty-IL-12/23, anty-IL-17, inhibitory kinaz JAK). Interleukiny 12 i 23 poprzez interakcje z receptorami uruchamiają ścieżkę sygnalizacyjną JAK/STAT, której Review aRticle/Praca Poglądowa signaling pathways associated with interleukins 12 and 23 and epigenetic mechanism of sequential-specific regulation of expression of related genes by mirnAs as molecular markers for assessing the potential of anti-cytokine therapies Ścieżki sygnalizacyjne związane z interleukiną 12 i 23 oraz epigenetyczny mechanizm sekwencyjnie specyficznej regulacji ekspresji związanych z nimi genów przez cząsteczki mirnA jako molekularne markery oceny potencjału terapii antycytokinowych

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Quantitative analysis of transforming growth factor beta isoforms mRNA TGF-β1-3 in the patients with psoriasis

Cited by 3 publications

References 0 publications

The Influence of Adalimumab and Cyclosporine A on the Expression Profile of the Genes Related to TGFβ Signaling Pathways in Keratinocyte Cells Treated with Lipopolysaccharide A

The Influence of Adalimumab and Cyclosporine A on the Expression Profile of the Genes Related to TGFβ Signaling Pathways in Keratinocyte Cells Treated with Lipopolysaccharide A

The impact of diabetes and metabolic syndromes to the effectiveness of cyclosporine a pharmacotherapy in psoriatic patients

Signaling pathways associated with interleukins 12 and 23 and epigenetic mechanism of sequential-specific regulation of expression of related genes by miRNAs as molecular markers for assessing the potential of anti-cytokine therapies

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