Effects of Histamine and the α-Tocopherol Metabolite α-13′-COOH in an Atopic Dermatitis Full-Thickness Skin Model

Affiliation
Department of Dermatology, University Hospital Jena, 07743 Jena, Germany
Riedl, Rebecca;
GND
1172048932
ORCID
0000-0003-3796-0729
Affiliation
Institute of Nutritional Science, Friedrich Schiller University Jena, 07743 Jena, Germany
Wallert, Maria;
GND
12292620X
ORCID
0000-0002-9649-840X
Affiliation
Institute of Nutritional Science, Friedrich Schiller University Jena, 07743 Jena, Germany
Lorkowski, Stefan;
GND
141238739
Affiliation
Department of Dermatology, University Hospital Jena, 07743 Jena, Germany
Wiegand, Cornelia

Atopic dermatitis is a T-cell mediated inflammatory skin disease with detected elevated levels of histamine in skin or plasma. In this study, the effects of histamine in a T H 2 cytokine environment on human keratinocytes and three-dimensional skin models were investigated. These models were used to explore the anti-inflammatory properties of the α-tocopherol-derived long-chain metabolite α-13’-carboxychromanol (α-13’-COOH). Histamine and T H 2 cytokine-induced proliferation of keratinocytes was studied using a scratch assay. The inflammatory marker interleukin-8 was significantly increased in healthy and T H 2 cytokine-stimulated keratinocytes and skin models after histamine treatment. The incubation of full-thickness skin models with T H 2 cytokines and histamine resulted in morphological changes in the epidermal layer, interpreted as hyperkeratosis. α-13’-COOH significantly decreased interleukin-8 in these disease-associated skin models. Histological staining of filaggrin showed skin-strengthening effects following α-13’-COOH treatment, without changes in mRNA expression. Cytokeratin 10 mRNA expression tended to be increased in response to α-13’-COOH. Anti-allergic properties of α-13’-COOH were studied by pre-incubation of human leukocytes with α-13’-COOH. This resulted in reduced sulfido-leukotriene synthesis. The hyperproliferation effect of histamine in atopic dermatitis skin models may be of further interest to the study of disease-associated morphological changes. Moreover, α-13’-COOH is a promising natural compound for the treatment of inflammatory skin diseases.

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