Artemin causes hypersensitivity to warm sensation, mimicking warmth-provoked pruritus in atopic dermatitis - 29/08/12
Abstract |
Background |
Itch impairs the quality of life for many patients with dermatoses, especially atopic dermatitis (AD), and is frequently induced by a warm environment.
Objective |
To determine the mechanism underlying itch induction by warmth, we focused on artemin, a member of glial cell line–derived neurotrophic factors (GDNFs).
Methods |
A gene array assay revealed that artemin was expressed in substance P–treated dermal fibroblasts. The expression of artemin in healthy and AD-lesional skin was evaluated with immunohistochemistry and in situ hybridization. The impact of fibroblast-derived artemin on the proliferation and morphology of neural cell was investigated in vitro. To confirm the involvement of artemin in skin sensibility, wild-type and GDNF family receptor ⍺3 knockout mice were employed for sensory examination.
Results |
Artemin-expressing fibroblasts accumulated in skin lesions of patients with AD. Artemin induced cell proliferation of a neuroblastoma cell line in vitro, and intradermal injection of artemin in mice resulted in peripheral nerve sprouting and thermal hyperalgesia. Artemin-treated mice demonstrated scratching behavior in a warm environment, but mice deficient for GDNF family receptor ⍺3, a potent artemin receptor, did not show this behavior. Furthermore, the escaping response to heat stimulus was attenuated in GDNF family receptor ⍺3 knockout mice, suggesting that artemin may contribute to sensitivity to heat.
Conclusion |
These data suggest that dermal fibroblasts secrete artemin in response to substance P, leading to abnormal peripheral innvervation and thermal hyperalgesia. We hypothesize that artemin lowers the threshold of temperature-dependent itch sensation and might therefore be a novel therapeutic target for treating pruritic skin disorders, including AD.
Le texte complet de cet article est disponible en PDF.Key words : Artemin, fibroblast, substance P, atopic dermatitis, itch, nerve fiber, warmth
Abbreviations used : AD, CM/SP, GDNF, GFR⍺, GFR⍺3 KO, NGF, NHDF, PDF, rARTN, SP, TRPV1
Plan
This study was supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan. |
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Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 130 - N° 3
P. 671 - septembre 2012 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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