PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV

Freie Vorträge
FV 5
Histamine modulates tight and desmosomal junction proteins in a human
organotypic skin model
Maria Gschwandtner 1
Michael Mildner 1
Veronika Mlitz 1
Florian Gruber 1
Leopold Eckhart 1
Thomas Werfel 2
Ralf Gutzmer 2
Peter M. Elias 3
1, 4
Erwin Tschachler
1 Medical University of Vienna, Department of Dermatology, Research Division of
Biology and Pathobiology of the Skin, Vienna, Austria
2 Hannover Medical School, Department of Dermatology, Hannover, Germany
3 University of San Francisco, Department of Dermatology, San Francisco, CA, USA
4 CE.R.I.E.S., Neuilly, Frankreich
Introduction: A close intercellular contact in the epidermis is normally maintained by
the expression of proteins that form the three types of epidermal junctions: tight,
desmosomal and adherens junctions. In several skin diseases, such as atopic dermatitis,
this network of intercellular junction proteins is disturbed, resulting in a functional
defect of the epidermal barrier. Recently, we found that histamine impairs epidermal
differentiation, a process linked to skin barrier formation. Therefore we investigated in
this study the effect of histamine on the expression of epidermal junction proteins.
Methods: We cultured human keratinocytes under differentiation promoting
conditions in monolayer and in organotypic skin model cultures in the presence of
histamine. The expression of epidermal junction components was determined by
real-time PCR, Western Blot and immunofluorescence staining. Epidermal lipid
composition was analyzed by thin layer chromatography and the barrier function of
organotypic skin models was tested with the application of tracer molecules.
Results: Addition of histamine to human keratinocytes grown in monolayer culture
and three-dimensional organotypic skin models reduced the expression of tight
junction components (occludin, tight junction protein-1, claudin-1 and claudin-4) and
desmosomal junction components (corneodesmosin, desmoglein-1 and demsocollin-1).
In contrast, the expression level of proteins forming adherens junctions and the
presence of the main lipid classes in the epidermis was not influenced by histamine.
Experiments with the tracer molecules lucifer yellow and biotin showed that histamine
perturbed the epidermal barrier formation in organotypic skin models mainly in the
granular layer at the level of tight and desmosomal junctions; while stratum corneum
permeability was not modified. Taken together these findings suggest a deteriorating
effect of histamine on the formation of epidermal intercellular junctions, possibly
contributing to the skin barrier defects observed in atopic dermatitis.
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