Manuka honey activates the aryl hydrocarbon receptor: Implications for skin inflammation.

Autor: Alangari AA; Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK. Electronic address: aangari@ksu.edu.sa., Ashoori MD; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK., Alwan W; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK., Dawe HR; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK., Stockinger B; AhRimmunity Lab, The Francis Crick Institute, NW1 1AA London, UK., Barker JN; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK., Wincent E; Institute of Environmental Medicine, The Karolinska Institute, Stockholm, Sweden., Di Meglio P; St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, London, UK. Electronic address: paola.dimeglio@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Pharmacological research [Pharmacol Res] 2023 Aug; Vol. 194, pp. 106848. Date of Electronic Publication: 2023 Jul 05.
DOI: 10.1016/j.phrs.2023.106848
Abstrakt: Manuka honey (MH) is a complex nutritional material with antimicrobial, antioxidant and anti-inflammatory activity. We have previously shown that MH down regulates IL-4-induced CCL26 expression in immortalized keratinocytes. As MH contains potential ligands of the Aryl Hydrocarbon Receptor (AHR), a key regulator of skin homeostasis, we hypothesize that this effect is mediated via AHR activation. Here, we treated HaCaT cell lines, either stable transfected with an empty vector (EV-HaCaT) or in which AHR had been stable silenced (AHR-silenced HaCaT); or primary normal human epithelial keratinocytes (NHEK) with 2% MH for 24 h. This induced a 15.4-fold upregulation of CYP1A1 in EV-HaCaTs, which was significantly reduced in AHR-silenced cells. Pre-treatment with the AHR antagonist CH223191 completely abrogated this effect. Similar findings were observed in NHEK. In vivo treatment of the Cyp1a1 Cre x R26R eYFP reporter mice strain's skin with pure MH significantly induced CYP1A1 expression compared with Vaseline. Treatment of HaCaT with 2% MH significantly decreased baseline CYP1 enzymatic activity at 3 and 6 h but increased it after 12 h, suggesting that MH may activate the AHR both through direct and indirect means. Importantly, MH downregulation of IL-4-induced CCL26 mRNA and protein was abrogated in AHR-silenced HaCaTs and by pre-treatment with CH223191. Finally, MH significantly upregulated FLG expression in NHEK in an AHR-dependent manner. In conclusion, MH activates AHR, both in vitro and in vivo, thereby providing a mechanism of its IL4-induced CCL26 downregulation and upregulation of FLG expression. These results have potential clinical implications for atopic diseases and beyond.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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