Glucocorticoid receptors GRα and GRβ are expressed in inflammatory dermatoses

Kubin, Minna E.; Hägg, Päivi M.; Kokkonen, Nina; Väyrynen, Juha P.; Haapasaari, Kirsi‐Maria; Moilanen, Jyri; Kallioinen, Matti; Hurskainen, Tiina; Tasanen, Kaisa

doi:10.1684/ejd.2015.2691

Cited by 18 publications

(25 citation statements)

References 37 publications

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“…Both therapies increased the expression of GRα mRNA in lesional skin, but the number of GRα immunopositive cells in skin samples and the GRα mRNA level in PBMCs were decreased. Taken together with the outcomes of our previous research (21,45), these findings suggest that the regulation of GRα expression may be a more complex process than previously thought. Unfortunately, the current study did not increase our understanding of the function, regulation and proposed inhibitory action of GRβ (31), since its expression varied greatly in both skin and PBMCs.…”

Section: Discussionsupporting

confidence: 76%

“…Reverse transcription was done using RevertAid reverse transcriptase (Thermo Fisher Scientific, Waltham, MA, USA). Quantitative real-time PCR (RT-qPCR) was performed as described previously (21) to quantify IL-6, IL-17A, IL-23A, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, T-box expressed in T cells (T-bet, TBX21), forkhead/winged helix transcription factor 3 (FoxP3), S100A7, chemokine ligand (CCL)-20 and glucocorticoid receptor GRα and GRβ transcripts. Human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and human β-actin served as controls.…”

Section: Total Rna Isolation and Quantitative Real-time Pcrmentioning

confidence: 99%

“…Immunohistochemical staining of skin biopsies and digital image analysis with CD3, CD4, CD8, FoxP3, IL-17A positive cells and GR isoforms was performed as earlier described (21,22). The antibodies are listed in Table SII 1 .…”

Section: Immunohistochemical Analysismentioning

confidence: 99%

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Clinical Efficiency of Topical Calcipotriol/Betamethasone Treatment in Psoriasis Relies on Suppression of the Inflammatory TNFα – IL-23 – IL-17 Axis

Kubin¹,

Kokkonen²,

Palatsi³

et al. 2017

Acta Derm Venerol

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The effects of topical calcipotriol/betamethasone combination therapy and betamethasone monotherapy on inflammatory T-cell numbers and molecular markers were compared in patients with psoriasis. Combination therapy down-regulated the expression of tumour necrosis factor (TNF)-α, interleukin (IL)-23A, IL-17A, S100A7, CCL-20 and interferon (IFN)-γ in skin and TNF-α, IL-6, IL-23A, T-bet and IFN-γ in peripheral blood mononuclear cells (PBMCs). Betamethasone monotherapy had less effect. Expression of FoxP3 in both skin and PBMCs was down-regulated by calcipotriol/betamethasone, but not by betamethasone. Immunohistochemical analysis revealed that calcipotriol/betamethasone reduced the numbers of CD4+ and CD8+ T cells and Tregs in psoriatic lesions more than betamethasone. Flow cytometric analyses demonstrated that calcipotriol/betamethasone decreased the numbers of circulating CD8+ T cells, Tregs, skin-homing Th17 memory cells and Th22 memory cells, while betamethasone had little or no effect. Glucocorticoid receptors GRα and GRß were expressed in psoriatic skin. In conclusion, calcipotriol increases the immunosuppressive power of betamethasone by suppressing the inflammatory TNF-α - IL-23 - IL-17 axis.

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Section: Discussionsupporting

confidence: 76%

Section: Total Rna Isolation and Quantitative Real-time Pcrmentioning

confidence: 99%

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Clinical Efficiency of Topical Calcipotriol/Betamethasone Treatment in Psoriasis Relies on Suppression of the Inflammatory TNFα – IL-23 – IL-17 Axis

Kubin¹,

Kokkonen²,

Palatsi³

et al. 2017

Acta Derm Venerol

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“…Glucocorticoid receptors (GR) exist in several isoforms. However, the isoforms GRα and GRβ are clinically considered as the most important and the upregulation of GRβ has been associated with GC insensitivity in many inflammatory diseases, such as asthma, rheumatoid arthritis and systemic lupus erythematosus . Conversely to GRα, GRβ does not bind glucocorticoid and functions as a dominant negative inhibitor, which antagonizes GRα activity.…”

Section: Introductionmentioning

confidence: 99%

Variation of the epidermal expression of glucocorticoid receptor‐beta as potential predictive marker of bullous pemphigoid outcome

Brulefert

Jan

Plée

et al. 2017

Experimental Dermatology

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Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease in Western countries. Although topical and/or systemic glucocorticoids treatment efficacy is widely recognized, up to 30% of patients with BP may undergo a relapse during the first year of treatment. We investigated the protein expression of the total glucocorticoid receptor and GRβ isoform in the skin biopsy specimens from patients with BP and wondered whether such investigation at baseline provided a tool to predict disease outcome. Total GR and GRβ protein expressions were detected by immunohistochemistry at baseline on 12 patients who later relapse and 11 patients who remained on remission in comparison with 14 control patients. The expression of GRβ in the epidermis of patients with BP who later relapse was significantly higher than that in the epidermis of patients with BP controlled upon corticosteroid treatment, which was also higher than control patients. Thus, our results suggest that increased protein expression of GRβ in skin epithelial cells is predictive of reduced steroid treatment efficacy, and therefore of increased risk of disease relapse in patients with BP.

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“…These isoforms are known to have different biological activities and to be differently regulated, so that the composition of these isoforms may differ according to the cell type and tissue. For example, GRβ is abundant in certain types of cells such as neutrophil and epithelial cell 1415. Glucocorticoid resistance seems to be mediated by a variety of pathways which influence different activities of the isoform composition.…”

mentioning

confidence: 99%