title: Glucocorticoid receptors GRα and GRβ are expressed in inflammatory dermatoses.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Minna E
authors.initials: ME
authors.lastname: Kubin
authors.affiliation: 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.
authors.forename: Päivi M
authors.initials: PM
authors.lastname: Hägg
authors.affiliation: 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.
authors.forename: Nina
authors.initials: N
authors.lastname: Kokkonen
authors.affiliation: Department of Pathology and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, FIN-90220, Oulu, Finland.
authors.forename: Juha P
authors.initials: JP
authors.lastname: Väyrynen
authors.affiliation: Department of Pathology, Oulu University Hospital and University of Oulu, FIN-90220, Oulu, Finland.
authors.forename: Kirsi-Maria
authors.initials: KM
authors.lastname: Haapasaari
authors.affiliation: 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.
authors.forename: Jyri
authors.initials: J
authors.lastname: Moilanen
authors.affiliation: Department of Pathology, Oulu University Hospital and University of Oulu, FIN-90220, Oulu, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Kallioinen
authors.affiliation: 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.
authors.forename: Tiina
authors.initials: T
authors.lastname: Hurskainen
authors.affiliation: 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.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Tasanen
mesh_terms: D000328:Adult; D003872:Dermatitis / Q000188:drug therapy / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000188:drug therapy / Q000378:metabolism; D004351:Drug Resistance; D004485:Eczema / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism; D008010:Lichen Planus / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009450:Neurodermatitis / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D011239:Prednisolone / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D011239:Prednisolone
keywords: atopic dermatitis; glucocorticoid receptor alpha; glucocorticoid receptor beta; glucocorticoid resistance; inflammatory dermatoses; neutrophil