title: House dust mite allergen exerts no direct proinflammatory effects on human keratinocytes.
abstract: BACKGROUND
  Dermatophagoides pteronyssinus is a trigger of atopic dermatitis. Many D pteronyssinus allergens are proteases that can elicit airway inflammation by stimulating the release of cytokines and chemokines by bronchial epithelial cells.
  
  
  OBJECTIVE
  We sought to investigate whether D pteronyssinus allergens can exert a similar activity on skin keratinocytes.
  
  
  METHODS
  Primary cultures of keratinocytes from healthy subjects or patients with atopic dermatitis and normal human bronchial epithelial cells were compared for cytokine production in response to D pteronyssinus extract.
  
  
  RESULTS
  Keratinocytes, but not bronchial epithelial cells, displayed a modest dose-dependent release of IL-1alpha and IL-1 receptor antagonist but no induction of their mRNA after exposure to D pteronyssinus. However, D pteronyssinus also degraded these cytokines. On the other hand, D pteronyssinus extract induced bronchial epithelial cells, but not keratinocytes, to increased expression of IL-8/CXCL8 and GM-CSF mRNA and protein. These effects were efficiently abrogated by a mixture of cysteine and serine protease inhibitors. Both IL-8 and GM-CSF were fully resistant to D pteronyssinus proteolytic attack. No induction of monocyte chemoattractant protein 1/CCL2, RANTES/CCL5, or IFN-gamma-induced protein of 10 kd/CXCL10 was detected in either cell type. Only bronchial epithelial cells expressed protease-activated receptor (PAR) 4 mRNA, whereas PAR-1, PAR-2, and PAR-3 mRNA was found in both cell types. D pteronyssinus did not affect PAR mRNA signals.
  
  
  CONCLUSIONS
  Although D pteronyssinus can cause proteolysis-dependent release of cytokines from keratinocytes, it appears incapable of activating de novo expression of cytokines and chemokines, arguing against a direct proinflammatory activity of house dust mite on the skin.
authors.affiliation: Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mascia
authors.forename: Valentina
authors.initials: V
authors.lastname: Mariani
authors.forename: Alberto
authors.initials: A
authors.lastname: Giannetti
authors.forename: Giampiero
authors.initials: G
authors.lastname: Girolomoni
authors.forename: Saveria
authors.initials: S
authors.lastname: Pastore
mesh_terms: D000328:Adult; D000818:Animals; D039741:Antigens, Dermatophagoides; D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000503:physiopathology; D004391:Dust / Q000009:adverse effects*; D004847:Epithelial Cells; D005260:Female; D006023:Glycoproteins / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007249:Inflammation; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology*; D008297:Male; D008925:Mites / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D016207:Cytokines; D004391:Dust; D006023:Glycoproteins