- 作者：Franziska Glatzer ; Maria Gschw ; tner ; Sarah Ehling ; Kristine Rossbach ; Katrin Janik ; Andreas Klos ; Wolfgang B盲umer ; Manfred Kietzmann ; Thomas Werfel ; Ralf Gutzmer
- 关键词：Histamine ; keratinocyte ; proliferation ; histamine 4 receptor ; human ; mouse ; atopic dermatitis
- 刊名：Journal of Allergy and Clinical Immunology
- 出版年：December, 2013
- 年：2013
- 卷：132
- 期：6
- 页码：1358-1367
- 全文大小：1918 K
Background
Epidermal hyperproliferation resulting in acanthosis is an important clinical observation in patients with atopic dermatitis, and its underlying mechanisms are not completely understood.Objective
Because increased levels of histamine are present in lesional skin, we investigated the effect of histamine, especially with regard to histamine 4 receptor (H4R) activation, on the proliferation of human and murine keratinocytes.
Methods
The expression of H4R on human and murine keratinocytes was detected by using real-time PCR. Keratinocyte proliferation was evaluated by using different
Results
We detected H4R mRNA on foreskin keratinocytes and on outer root sheath keratinocytes; H4R mRNA was more abundant in keratinocytes from patients with atopic dermatitis compared with those from nonatopic donors. Stimulation of foreskin keratinocytes, atopic dermatitis outer root sheath keratinocytes, and H4R-transfected HaCaT cells with histamine and H4R agonist resulted in an increase in proliferation, which was blocked with the H4R-specific antagonist JNJ7777120. Abdominal epidermis of H4R-deficient mice was significantly thinner, and the
Conclusion
H4R is highly expressed on keratinocytes from patients with atopic dermatitis, and its stimulation induces keratinocyte proliferation. This might represent a mechanism that contributes to the epidermal hyperplasia observed in patients with atopic dermatitis.