The histamine-synthesizing enzyme histidine decarboxylase is upregulated by keratinocytes in atopic skin

© 2014 British Association of Dermatologists. 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. Objectives 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. What's already known about this topic? Keratinocytes express the histamine-synthesizing enzyme, histidine decarboxylase (HDC), under ultraviolet B and surfactant exposure. What does this study add? HDC expression in keratinocytes is increased in atopic dermatitis. Cytokines, lipopolysaccharide and house dust mites increase HDC levels; this leads to increased histamine content in keratinocytes. Endogenously expressed histamine affects keratinocyte differentiation.