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Epicutaneous Sensitization to the Phytocannabinoid β-Caryophyllene Induces Pruritic Inflammation

In recent years, there has been increased accessibility to cannabis for recreational and medicinal use. Incidentally, there has been an increase in reports describing allergic reactions to cannabis including exacerbation of underlying asthma. Recently, multiple protein allergens were discovered in c...

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Detalles Bibliográficos
Autores principales: Inan, Saadet, Ward, Sara J., Baltazar, Citlalli T., Peruggia, Gabrielle A., Javed, Elham, Nayak, Ajay P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10532273/
https://www.ncbi.nlm.nih.gov/pubmed/37762646
http://dx.doi.org/10.3390/ijms241814328
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author Inan, Saadet
Ward, Sara J.
Baltazar, Citlalli T.
Peruggia, Gabrielle A.
Javed, Elham
Nayak, Ajay P.
author_facet Inan, Saadet
Ward, Sara J.
Baltazar, Citlalli T.
Peruggia, Gabrielle A.
Javed, Elham
Nayak, Ajay P.
author_sort Inan, Saadet
collection PubMed
description In recent years, there has been increased accessibility to cannabis for recreational and medicinal use. Incidentally, there has been an increase in reports describing allergic reactions to cannabis including exacerbation of underlying asthma. Recently, multiple protein allergens were discovered in cannabis, yet these fail to explain allergic sensitization in many patients, particularly urticaria and angioedema. Cannabis has a rich chemical profile including cannabinoids and terpenes that possess immunomodulatory potential. We examined whether major cannabinoids of cannabis such as cannabidiol (CBD) and the bicyclic sesquiterpene beta-caryophyllene (β-CP) act as contact sensitizers. The repeated topical application of mice skin with β-CP at 10 mg/mL (50 µL) induced an itch response and dermatitis at 2 weeks in mice, which were sustained for the period of study. Histopathological analysis of skin tissues revealed significant edema and desquamation for β-CP at 10 mg/mL. For CBD and β-CP, we observed a dose-dependent increase in epidermal thickening with profound thickening observed for β-CP at 10 mg/mL. Significant trafficking of CD11b cells was observed in various compartments of the skin in response to treatment with β-CP in a concentration-dependent manner. Mast cell trafficking was restricted to β-CP (10 mg/mL). Mouse proteome profiler cytokine/chemokine array revealed upregulation of complement C5/5a (anaphylatoxin), soluble intracellular adhesion molecule-1 (sICAM-1) and IL-1 receptor antagonist (IL-1RA) in animals dosed with β-CP (10 mg/mL). Moreover, we observed a dose-dependent increase in serum IgE in animals dosed with β-CP. Treatment with β-CP (10 mg/mL) significantly reduced filaggrin expression, an indicator of barrier disruption. In contrast, treatment with CBD at all concentrations failed to evoke scratching and dermatitis in mice and did not result in increased serum IgE. Further, skin tissues were devoid of any remarkable features, although at 10 mg/mL CBD we did observe the accumulation of dermal CD11b cells in skin tissue sections. We also observed increased filaggrin staining in mice repeatedly dosed with CBD (10 mg/mL). Collectively, our studies indicate that repeated exposure to high concentrations of β-CP can induce dermatitis-like pathological outcomes in mice.
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spelling pubmed-105322732023-09-28 Epicutaneous Sensitization to the Phytocannabinoid β-Caryophyllene Induces Pruritic Inflammation Inan, Saadet Ward, Sara J. Baltazar, Citlalli T. Peruggia, Gabrielle A. Javed, Elham Nayak, Ajay P. Int J Mol Sci Article In recent years, there has been increased accessibility to cannabis for recreational and medicinal use. Incidentally, there has been an increase in reports describing allergic reactions to cannabis including exacerbation of underlying asthma. Recently, multiple protein allergens were discovered in cannabis, yet these fail to explain allergic sensitization in many patients, particularly urticaria and angioedema. Cannabis has a rich chemical profile including cannabinoids and terpenes that possess immunomodulatory potential. We examined whether major cannabinoids of cannabis such as cannabidiol (CBD) and the bicyclic sesquiterpene beta-caryophyllene (β-CP) act as contact sensitizers. The repeated topical application of mice skin with β-CP at 10 mg/mL (50 µL) induced an itch response and dermatitis at 2 weeks in mice, which were sustained for the period of study. Histopathological analysis of skin tissues revealed significant edema and desquamation for β-CP at 10 mg/mL. For CBD and β-CP, we observed a dose-dependent increase in epidermal thickening with profound thickening observed for β-CP at 10 mg/mL. Significant trafficking of CD11b cells was observed in various compartments of the skin in response to treatment with β-CP in a concentration-dependent manner. Mast cell trafficking was restricted to β-CP (10 mg/mL). Mouse proteome profiler cytokine/chemokine array revealed upregulation of complement C5/5a (anaphylatoxin), soluble intracellular adhesion molecule-1 (sICAM-1) and IL-1 receptor antagonist (IL-1RA) in animals dosed with β-CP (10 mg/mL). Moreover, we observed a dose-dependent increase in serum IgE in animals dosed with β-CP. Treatment with β-CP (10 mg/mL) significantly reduced filaggrin expression, an indicator of barrier disruption. In contrast, treatment with CBD at all concentrations failed to evoke scratching and dermatitis in mice and did not result in increased serum IgE. Further, skin tissues were devoid of any remarkable features, although at 10 mg/mL CBD we did observe the accumulation of dermal CD11b cells in skin tissue sections. We also observed increased filaggrin staining in mice repeatedly dosed with CBD (10 mg/mL). Collectively, our studies indicate that repeated exposure to high concentrations of β-CP can induce dermatitis-like pathological outcomes in mice. MDPI 2023-09-20 /pmc/articles/PMC10532273/ /pubmed/37762646 http://dx.doi.org/10.3390/ijms241814328 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Inan, Saadet
Ward, Sara J.
Baltazar, Citlalli T.
Peruggia, Gabrielle A.
Javed, Elham
Nayak, Ajay P.
Epicutaneous Sensitization to the Phytocannabinoid β-Caryophyllene Induces Pruritic Inflammation
title Epicutaneous Sensitization to the Phytocannabinoid β-Caryophyllene Induces Pruritic Inflammation
title_full Epicutaneous Sensitization to the Phytocannabinoid β-Caryophyllene Induces Pruritic Inflammation
title_fullStr Epicutaneous Sensitization to the Phytocannabinoid β-Caryophyllene Induces Pruritic Inflammation
title_full_unstemmed Epicutaneous Sensitization to the Phytocannabinoid β-Caryophyllene Induces Pruritic Inflammation
title_short Epicutaneous Sensitization to the Phytocannabinoid β-Caryophyllene Induces Pruritic Inflammation
title_sort epicutaneous sensitization to the phytocannabinoid β-caryophyllene induces pruritic inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10532273/
https://www.ncbi.nlm.nih.gov/pubmed/37762646
http://dx.doi.org/10.3390/ijms241814328
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