Kubin Minna E, Hägg Päivi M, Kokkonen Nina, Väyrynen Juha P, Haapasaari Kirsi-Maria, Moilanen Jyri, Kallioinen Matti, Hurskainen Tiina, Tasanen Kaisa
PEDEGO Research Center, Oulu Center for Cell-Matrix Research, Department of Dermatology and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FIN-90220, Oulu, Finland.
Department of Pathology and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FIN-90220, Oulu, Finland.
Eur J Dermatol. 2016 Jan-Feb;26(1):21-7. doi: 10.1684/ejd.2015.2691.
Glucocorticoids (GC) are the most commonly used anti-inflammatory drugs in dermatology. The actions of GCs are mediated by the glucocorticoid receptor (GR). Alternative splicing of GR mRNA gives rise to different isoforms, GRα and GRβ being the most important. GRβ antagonizes the activity of GRα and its up-regulation has been associated with glucocorticoid insensitivity in several non-cutaneous inflammatory diseases.
Using immunohistochemical stainings, we analyzed the expression of GRα and GRβ in lesional skin samples of patients with atopic dermatitis, lichen ruber planus, eczema nummulare and lichen simplex chronicus. We also conducted a study of 13 severe atopic patients to investigate the effect of prednisolone treatment on the expression of GR isoforms using quantitative PCR, western blot and immunohistochemical analysis.
GRα and GRβ were expressed in atopic dermatitis, lichen ruber planus, eczema nummulare and lichen simplex chronicus. Our novel finding was that GRβ is abundant in keratinocytes and cutaneous neutrophils. Nuclear staining of both GRα and GRβ was strongest in keratinocytes of patients with lichen ruber planus, whereas the least nuclear positivity was detected in keratinocytes of patients with atopic dermatitis. In severe atopic dermatitis GRα and GRβ were expressed in both peripheral blood mononuclear cells and the skin. The expression of GRα and GRβ varied during prednisolone therapy but the changes were not related to treatment response or GC insensitivity.
GRα and GRβ are expressed in inflammatory dermatoses. In severe atopic dermatitis the increased expression of GRβ mRNA is not connected to insensitivity against prednisolone treatment.
糖皮质激素（GC）是皮肤科最常用的抗炎药物。GC的作用由糖皮质激素受体（GR）介导。GR mRNA的可变剪接产生不同的异构体，其中GRα和GRβ最为重要。GRβ拮抗GRα的活性，在几种非皮肤炎症性疾病中，其上调与糖皮质激素不敏感有关。
我们采用免疫组织化学染色法，分析了特应性皮炎、扁平苔藓、钱币状湿疹和慢性单纯性苔藓患者皮损样本中GRα和GRβ的表达。我们还对13例重度特应性患者进行了研究，采用定量PCR、western印迹和免疫组织化学分析，探讨泼尼松龙治疗对GR异构体表达的影响。
GRα和GRβ在特应性皮炎、扁平苔藓、钱币状湿疹和慢性单纯性苔藓中均有表达。我们的新发现是，GRβ在角质形成细胞和皮肤中性粒细胞中含量丰富。在扁平苔藓患者的角质形成细胞中，GRα和GRβ的核染色最强，而在特应性皮炎患者的角质形成细胞中，核阳性最少。在重度特应性皮炎中，GRα和GRβ在外周血单个核细胞和皮肤中均有表达。在泼尼松龙治疗期间，GRα和GRβ的表达有所变化，但这些变化与治疗反应或GC不敏感无关。
GRα和GRβ在炎症性皮肤病中表达。在重度特应性皮炎中，GRβ mRNA表达增加与对泼尼松龙治疗不敏感无关。
