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Substance P restores normal skin architecture and reduces epidermal infiltration of sensory nerve fiber in TNCB-induced atopic dermatitis-like lesions in NC/Nga mice.
- Source :
-
Journal of dermatological science [J Dermatol Sci] 2018 Mar; Vol. 89 (3), pp. 248-257. Date of Electronic Publication: 2017 Dec 01. - Publication Year :
- 2018
-
Abstract
- Background: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense pruritus and eczematous lesion. Substance P (SP) is an 11-amino-acid endogenous neuropeptide that belongs to the tachykinin family and several reports recently have supported the anti-inflammatory and tissue repairing roles of SP.<br />Objective: In this study, we investigated whether SP can improve AD symptoms, especially the impaired skin barrier function, in 2, 4, 6-trinitrochlorobenzene (TNCB)-induced chronic dermatitis of NC/Nga mice or not.<br />Method: AD-like dermatitis was induced in NC/Nga mice by repeated sensitization with TNCB for 5 weeks. The experimental group designations and topical treatments were as follows: vehicle group (AD-VE); SP group (AD-SP); and SP with NK1R antagonist CP99994 (AD-SP-A) group. Histological analysis was performed to evaluate epidermal differentiation, dermal integrity, and epidermal nerve innervation in AD-like lesions. The skin barrier functions and pruritus of NC/Nga mice were evaluated by measuring transepidermal water loss (TEWL) and scratching behavior, respectively.<br />Result: Topical SP treatment resulted in significant down-regulation of Ki67 and the abnormal-type keratins (K) K6, K16, and K17, restoration of filaggrin and claudin-1, marked reduction of TEWL, and restoration of basement membrane and dermal collagen deposition, even under continuous sensitization of low dose TNCB. In addition, SP significantly reduced innervation of itch-evoking nerve fibers, gelatinase activity and nerve growth factor (NGF) expression in the epidermis but upregulated semaphorin-3A (Sema3A) expression in the epidermis, along with reduced scratching behavior in TNCB-treated NC/Nga mice. All of these effects were completely reversed by co-treatment with the NK1R antagonist CP99994. In cultured human keratinocytes, SP treatment reduced expression of TGF-α, but upregulated TGF-β and Sema3A.<br />Conclusion: Topically administered SP can restore normal skin barrier function, reduce epidermal infiltration of itch-evoking nerve fibers in the AD-like skin lesions, and alleviate scratching behavior. Thus, SP may be proposed as a potential medication for chronic dermatitis and AD.<br /> (Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Body Water metabolism
Cells, Cultured
Dermatitis, Atopic metabolism
Dermatitis, Atopic pathology
Epidermis innervation
Epidermis pathology
Filaggrin Proteins
Male
Mice
Nerve Growth Factor analysis
Picryl Chloride
Pruritus drug therapy
Pruritus pathology
Semaphorin-3A analysis
Skin metabolism
Substance P pharmacology
Dermatitis, Atopic drug therapy
Epidermis drug effects
Nerve Fibers pathology
Skin drug effects
Substance P therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1873-569X
- Volume :
- 89
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of dermatological science
- Publication Type :
- Academic Journal
- Accession number :
- 29269174
- Full Text :
- https://doi.org/10.1016/j.jdermsci.2017.11.013