Journal
JOURNAL OF DERMATOLOGICAL SCIENCE
Volume 88, Issue 1, Pages 126-133Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2017.05.009
Keywords
Transient receptor potential vanilloid 1; Ultraviolet; Matrix metalloproteinases; Pro-inflammatory cytokines
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Funding
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI14C1277]
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Background: Transient receptor potential type 1 (TRPV1) can be activated by ultraviolet (UV) irradiation, and mediates UV-induced matrix metalloproteinase (MMP)-1 and proinflammatory cytokines in keratinocytes. Various chemicals and compounds targeting TRPV1 activation have been developed, but are not in clinical use mostly due to their safety issues. Objective: We aimed to develop a novel TRPV1-targeting peptide to inhibit UV-induced responses in human skin. Methods: We designed and generated a novel TRPV1 inhibitory peptide (TIP) which mimics the specific site in TRPV1 (aa 701-709: Gln-Arg-Ala-Ile-Thr-Ile-Leu-Asp-Thr, QRAITILDT), Thr(705), and tested its efficacy of blocking UV-induced responses in HaCaT, mouse, and human skin. Results: TIP effectively inhibited capsaicin-induced calcium influx and TRPV1 activation. Treatment of HaCaT with TIP prevented UV-induced increases of MMP-1 and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-alpha. In mouse skin in vivo, TIP inhibited UV-induced skin thickening and prevented UV-induced expression of MMP-13 and MMP-9. Moreover, TIP attenuated UV induced erythema and the expression of MMP-1, MMP-2, IL-6, and IL-8 in human skin in vivo. Conclusion: The novel synthetic peptide targeting TRPV1 can ameliorate UV-induced skin responses in vitro and in vivo, providing a promising therapeutic approach against UV-induced inflammation and photoaging. (C) 2017 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
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