title: Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis.
abstract: BACKGROUND
  Prurigo nodularis (PN) is a chronic dermatitis characterized by discrete, raised, and firm papulonodules with intense pruritus. The pathogenesis still remains to be elucidated.
  
  
  OBJECTIVE
  To clarify the role of Th1 and Th2 cytokines in the pathogenesis of PN.
  
  
  METHODS
  We examined the cytokine signatures, such as phosphorylation of STAT1, STAT3 and STAT6, HLA-DR and hyaluronan accumulation, to reveal the Th1 and Th2 cytokine influence on the lesional epidermis of PN.
  
  
  RESULTS
  We first optimized antigen retrieval methods to detect these signatures with antibodies for phospho-STAT1 (pSTAT1), phospho-STAT3 (pSTAT3), phospho-STAT6 (pSTAT6), HLA-DR and hyaluronic acid binding protein (HABP) on the formalin-fixed paraffin-embedded sections of psoriasis, lichen planus and atopic dermatitis biopsy samples. Activation of STAT1 and STAT6 in epidermis by Th1 and Th2 cytokines was further confirmed in a cultured skin equivalent model treated with interferon-γ or interleukin (IL)-4/IL-13. With the relevant immunostaining methods, we examined the cytokine signatures in 22 cases of PN. The results revealed that (i) the entire epidermis of 19 cases was stained with anti-pSTAT6 antibody, (ii) 21 cases demonstrated nuclear staining with anti-pSTAT3 antibody, (iii) the entire epidermis of 21 cases was stained with HABP, (iv) the epidermis of eight cases showed scattered staining with anti-pSTAT1 antibody, and (v) six cases were positive for HLA-DR membrane expression.
  
  
  CONCLUSIONS
  These data indicated that Th2 cytokines related to STAT6 activation together with some unknown stimuli that activate STAT3 play a principal role in the pathogenesis of PN.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Miyagi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fukushi
authors.forename: K
authors.initials: K
authors.lastname: Yamasaki
authors.forename: S
authors.initials: S
authors.lastname: Aiba
mesh_terms: D002466:Cell Nucleolus / Q000737:chemistry*; D016207:Cytokines / Q000502:physiology*; D004817:Epidermis / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D010766:Phosphorylation; D011536:Prurigo / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D018960:Hyaluronan Receptors; D018793:Interleukin-13; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050800:STAT6 Transcription Factor; D015847:Interleukin-4; D007371:Interferon-gamma; D006820:Hyaluronic Acid