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, GR alpha and GR beta being the most important. GR beta antagonizes the activity of GR alpha 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 GR alpha and GR beta 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:. GR alpha and GR beta were expressed in atopic dermatitis, lichen ruber planus, eczema nummulare and lichen simplex chronicus. Our novel finding was that GR beta is abundant in keratinocytes and cutaneous neutrophils. Nuclear staining of both GR alpha and GR beta 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 GR alpha and GR beta were expressed in both peripheral blood mononuclear cells and the skin. The expression of GR alpha and GR beta varied during prednisolone therapy but the changes were not related to treatment response or GC insensitivity. Conclusion: GR alpha and GR beta are expressed in inflammatory dermatoses. In severe atopic dermatitis the increased expression of GR beta mRNA is not connected to insensitivity against prednisolone treatment.