Histamine induces proliferation in keratinocytes from patients with atopic dermatitis through the histamine 4 receptor.
J Allergy Clin Immunol
; 132(6): 1358-67, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-23932072
ABSTRACT
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 in vitro cell proliferation assays, scratch assays, and measurement of the epidermal thickness of murine skin.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 in vitro proliferation of keratinocytes derived from H4R-deficient mice was lower compared with that seen in control mice. Interestingly, we only detected H4R expression on murine keratinocytes after stimulation with LPS and peptidoglycan.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.Palavras-chave
4-MH; 4-Methylhistamine; GAPDH; Glyceraldehyde-3-phosphate dehydrogenase; H1R; H2R; H3R; H4R; Histamine; Histamine 1 receptor; Histamine 2 receptor; Histamine 3 receptor; Histamine 4 receptor; Neonatal keratinocyte; Outer root sheath keratinocyte; atopic dermatitis; histamine 4 receptor; human; keratinocyte; mouse; nKC; orsKC; proliferation
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Receptores Histamínicos
/
Queratinócitos
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Receptores Acoplados a Proteínas G
/
Dermatite Atópica
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article