Chung, K, Pitcher, T, Grant, AD et al. (3 more authors) (2019) Cathepsin S acts via protease-activated receptor 2 to activate sensory neurons and induce itch-like behaviour. Neurobiology of Pain, 6. 100032. ISSN 2452-073X
Abstract
Chronic itch is a debilitating condition characterised by excessive scratching and is a symptom frequently reported in skin diseases such as atopic dermatitis. It has been proposed that release of the cysteine protease Cathepsin S (CatS) from skin keratinocytes or immune cells resident in or infiltrating the skin could act as a pruritogen in chronic itch conditions. CatS is known to activate protease-activated receptor 2 (PAR2). We therefore hypothesised that enzymatic activation of neuronally expressed PAR2 by CatS was responsible for activation of sensory neurons and transmission of itch signals. Intradermally-injected human recombinant (hr)-CatS or the PAR2 agonist, SLIGRL-NH2 behaved as pruritogens by causing scratching behaviour in mice. Hr-CatS-induced scratching behaviour was prevented by CatS inhibitors and PAR2 antagonists and reduced by 50% in TRPV1−/− mice compared with wild-type mice, whilst no significant reduction in scratching behaviour was observed in TRPA1−/− mice. Cultured dorsal root ganglion (DRG) cells showed an increase in [Ca2+]i following incubation with hr-CatS, and the percentage of neurons that responded to hr-CatS decreased in the presence of a PAR2 antagonist or in cultures of neurons from TRPV1−/− mice. Taken together, our results indicate CatS acts as a pruritogen via PAR2 activation in TRPV1-expressing sensory neurons.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | Itch; Proteases; Sensory neurons |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 02 May 2019 14:59 |
Last Modified: | 25 Jun 2023 21:48 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.ynpai.2019.100032 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:145542 |