PAR2, Keratinocytes, and Cathepsin S Mediate the Sensory Effects of Ciguatoxins Responsible for Ciguatera Poisoning.

Autor:	L'Herondelle K; Laboratoire Interactions Epitheliums Neurones, University of Brest, Brest, France., Pierre O; Laboratoire Interactions Epitheliums Neurones, University of Brest, Brest, France., Fouyet S; Laboratoire Interactions Epitheliums Neurones, University of Brest, Brest, France., Leschiera R; Laboratoire Interactions Epitheliums Neurones, University of Brest, Brest, France., Le Gall-Ianotto C; Laboratoire Interactions Epitheliums Neurones, University of Brest, Brest, France., Philippe R; Canalopathies et Signalisation Calcique, INSERM, University of Brest, Brest, France., Buscaglia P; Lymphocytes B et auto-immunité, INSERM, University of Brest, Brest, France., Mignen O; Canalopathies et Signalisation Calcique, INSERM, University of Brest, Brest, France; Lymphocytes B et auto-immunité, INSERM, University of Brest, Brest, France., Talagas M; Laboratoire Interactions Epitheliums Neurones, University of Brest, Brest, France; Department of Dermatology, University Hospital of Brest, Brest, France., Lewis RJ; Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia., Michel L; Onco-dermatologie, immunologie et cellules souches cutanées, INSERM, Paris, France., Misery L; Laboratoire Interactions Epitheliums Neurones, University of Brest, Brest, France; Department of Dermatology, University Hospital of Brest, Brest, France., Le Garrec R; Laboratoire Interactions Epitheliums Neurones, University of Brest, Brest, France. Electronic address: rlegarrec@univ-brest.fr.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2021 Mar; Vol. 141 (3), pp. 648-658.e3. Date of Electronic Publication: 2020 Aug 13.
DOI:	10.1016/j.jid.2020.07.020
Abstrakt:	Ciguatera fish poisoning is caused by the consumption of fish contaminated with ciguatoxins (CTXs). The most distressing symptoms are cutaneous sensory disturbances, including cold dysesthesia and itch. CTXs are neurotoxins known to activate voltage-gated sodium channels, but no specific treatment exists. Peptidergic neurons have been critically involved in ciguatera fish poisoning sensory disturbances. Protease-activated receptor-2 (PAR2) is an itch- and pain-related G protein‒coupled receptor whose activation leads to a calcium-dependent neuropeptide release. In this study, we studied the role of voltage-gated sodium channels, PAR2, and the PAR2 agonist cathepsin S in the cytosolic calcium increase and subsequent release of the neuropeptide substance P elicited by Pacific CTX-2 (P-CTX-2) in rat sensory neurons and human epidermal keratinocytes. In sensory neurons, the P-CTX-2‒evoked calcium response was driven by voltage-gated sodium channels and PAR2-dependent mechanisms. In keratinocytes, P-CTX-2 also induced voltage-gated sodium channels and PAR2-dependent marked calcium response. In the cocultured cells, P-CTX-2 significantly increased cathepsin S activity, and cathepsin S and PAR2 antagonists almost abolished P-CTX-2‒elicited substance P release. Keratinocytes synergistically favored the induced substance P release. Our results demonstrate that the sensory effects of CTXs involve the cathepsin S-PAR2 pathway and are potentiated by their direct action on nonexcitable keratinocytes through the same pathway. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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