title: The histamine-synthesizing enzyme histidine decarboxylase is upregulated by keratinocytes in atopic skin.
abstract: BACKGROUND
  Histamine is an abundant mediator accumulating in the skin of atopic patients, where it is thought to be derived from immune cells. While keratinocytes express histidine decarboxylase (HDC), levels of the enzyme in normal or diseased epidermis and factors that influence its expression in human keratinocytes are not known.
  
  
  OBJECTIVE
  To assess levels of HDC in inflammatory skin diseases and factors influencing its expression.
  
  
  METHODS
  Normal and filaggrin-insufficient human keratinocytes, organotypic epidermal models and skin samples were investigated for the expression of HDC. The effect of cytokines, bacterial and allergen stimuli exposure and functional changes in differentiation were evaluated in vitro.
  
  
  RESULTS
  We detected abundant expression of the HDC protein in all models studied; expression was increased in atopic skin samples. Filaggrin-insufficient keratinocytes maintained HDC levels, but exposure of keratinocytes to thymic stromal lymphopoietin, tumour necrosis factor-α, lipopolysaccharide (LPS) and house dust mite (HDM) extract increased HDC expression in vitro. Furthermore, filaggrin expression in cultured keratinocytes increased following histamine depletion.
  
  
  CONCLUSIONS
  Keratinocytes express abundant HDC protein, and the levels increase in atopic skin. LPS, HDM and cytokines, which are implicated in allergic inflammation, promote the expression of the enzyme and upregulate histamine levels in keratinocytes. Actively produced histamine influences keratinocyte differentiation, suggesting functional relevance of the axis to atopic dermatitis. The findings therefore identify a new point of therapeutic intervention.
authors: MRC Human Immunology Unit, NIHR Biomedical Research Centre, University of Oxford, John Radcliffe Hospital, Weatherall Institute of Molecular Medicine, Oxford, OX3 9DS, U.K.
authors: D
authors: D
authors: Gutowska-Owsiak
authors: L
authors: L
authors: Greenwald
authors: C
authors: C
authors: Watson
authors: T A
authors: TA
authors: Selvakumar
authors: X
authors: X
authors: Wang
authors: G S
authors: GS
authors: Ogg
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D003876:Dermatitis, Atopic / Q000201:enzymology*; D004485:Eczema / Q000201:enzymology; D004817:Epidermis / Q000201:enzymology; D000091344:Filaggrin Proteins; D006640:Histidine Decarboxylase / Q000378:metabolism*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000172:deficiency; D015603:Keratinocytes / Q000201:enzymology*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D006640:Histidine Decarboxylase