期刊
JOURNAL OF DERMATOLOGICAL SCIENCE
卷 66, 期 1, 页码 37-43出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2012.01.007
关键词
Atopic dermatitis; Epidermal keratinocytes; Nerve fibers; Pruritus; Sema3A
类别
资金
- Japanese Ministry of Health, Labour and Welfare
- KAKENHI [20790818]
- High-Tech Research Center Project for Private Universities
- MEXT
- Grants-in-Aid for Scientific Research [20790818, 10J04599] Funding Source: KAKEN
Background: Epidermal hyperinnervation in atopic dermatitis (AD) is activated directly by various external stimuli, causing enhanced itching. Nerve density is regulated by the nerve repulsion factor semaphorin 3A (Sema3A), along with nerve elongation factors. Objective: To investigate the effects of Sema3A ointment in the NC/Nga mouse model of AD. Methods: An AD-like phenotype was induced by repeated application of Dermatophagoides farinae body (Dfb) ointment to the dorsal skin of NC/Nga mice. Vaseline, heparinoid, betamethasone, tacrolimus and recombinant Sema3A ointments were applied to the lesional skin once a day for 4 days. Transepidermal water loss (TEWL) was measured before and after each treatment. We also scored the degree of dermatitis and recorded videos to observe scratching behavior. Subsequently, we collected skin samples from these mice for histological analyses. Results: Topical application of Sema3A, betamethasone and tacrolimus ointments significantly inhibited scratching behavior and improved dermatitis scores in Dfb-treated mice compared with control mice, whereas vaseline and heparinoid had no effects. A significant improvement of TEWL was observed only in Sema3A ointment-treated mice. Moreover, Sema3A ointment reduced the densities of PGP9.5- and substance P-immunoreactive nerve fibers in the epidermis and the numbers of inflammatory cells, such as CD4 immunoreactive T cells and eosinophils, and improved acanthosis in the Dfb-treated mice compared with controls. Conclusion: Sem3A ointment may have therapeutic efficacy in patients with pruritus and dermatitis of AD. (C) 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
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