Glucocorticoid Receptors GRα and GRβ Are Expressed in Inflammatory Dermatoses

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.