title: Matriptase-1 expression is lost in psoriatic skin lesions and is downregulated by TNFα in vitro.
abstract: OBJECTIVE
  Matriptase-1 participates in terminal keratinocyte (KC) differentiation. Knockdown of matriptase-1 in skin equivalent cultures leads to impaired KC differentiation and retention of nuclei in the stratum corneum. Here, we investigated the expression and regulation of matriptase-1 in psoriatic skin and in KC in vitro.
  
  
  METHODS
  Matriptase-1 expression in healthy and psoriatic skin and its regulation in skin equivalents were analyzed by Western blotting, immunofluorescence staining, qRT-PCR, and activity assays. Involvement of the nuclear factor kappa B (NFκB) signaling pathway was investigated by adenoviral overexpression of a dominant-negative form of IKK2.
  
  
  RESULTS
  Matriptase-1 expression was detected in the stratum granulosum of healthy human skin and in skin equivalent cultures. Its expression and activity was strongly reduced in lesional skin of patients with psoriasis. Addition of TNFα to skin equivalent cultures resulted in complete loss of matriptase-1 expression accompanied by disturbed KC differentiation. Mechanistically, we were able to show that TNFα-induced downregulation of matriptase-1 was inhibited by blocking the IKK2/NFκB signaling pathway.
  
  
  CONCLUSIONS
  Given that matriptase-1 participates in terminal KC differentiation, its absence in psoriatic skin lesions indicates that this contributes to the barrier disturbances in this disease. Our data suggests that blocking the IKK2/NFκB-pathway represents a potential target for the treatment of psoriasis.
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Mildner
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bauer
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Mlitz
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ballaun
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
mesh_terms: D002478:Cells, Cultured; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D012697:Serine Endopeptidases / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D012697:Serine Endopeptidases; C485596:ST14 protein, human