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Research ArticleInflammation, Immunopharmacology, and Asthma

Anti-inflammatory Properties of Cannabidiol, a Nonpsychotropic Cannabinoid, in Experimental Allergic Contact Dermatitis

Stefania Petrosino, Roberta Verde, Massimo Vaia, Marco Allarà, Teresa Iuvone and Vincenzo Di Marzo
Journal of Pharmacology and Experimental Therapeutics June 2018, 365 (3) 652-663; DOI: https://doi.org/10.1124/jpet.117.244368
Stefania Petrosino
Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli, Napoli, Italy (S.P., R.V., M.A., V.D.); Epitech Group SpA, Saccolongo, Padova, Italy (S.P., M.A.); and Dipartimento di Farmacologia Sperimentale, Università di Napoli “Federico II”, Napoli, Italy (M.V., T.I.)
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Roberta Verde
Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli, Napoli, Italy (S.P., R.V., M.A., V.D.); Epitech Group SpA, Saccolongo, Padova, Italy (S.P., M.A.); and Dipartimento di Farmacologia Sperimentale, Università di Napoli “Federico II”, Napoli, Italy (M.V., T.I.)
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Massimo Vaia
Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli, Napoli, Italy (S.P., R.V., M.A., V.D.); Epitech Group SpA, Saccolongo, Padova, Italy (S.P., M.A.); and Dipartimento di Farmacologia Sperimentale, Università di Napoli “Federico II”, Napoli, Italy (M.V., T.I.)
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Marco Allarà
Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli, Napoli, Italy (S.P., R.V., M.A., V.D.); Epitech Group SpA, Saccolongo, Padova, Italy (S.P., M.A.); and Dipartimento di Farmacologia Sperimentale, Università di Napoli “Federico II”, Napoli, Italy (M.V., T.I.)
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Teresa Iuvone
Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli, Napoli, Italy (S.P., R.V., M.A., V.D.); Epitech Group SpA, Saccolongo, Padova, Italy (S.P., M.A.); and Dipartimento di Farmacologia Sperimentale, Università di Napoli “Federico II”, Napoli, Italy (M.V., T.I.)
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Vincenzo Di Marzo
Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli, Napoli, Italy (S.P., R.V., M.A., V.D.); Epitech Group SpA, Saccolongo, Padova, Italy (S.P., M.A.); and Dipartimento di Farmacologia Sperimentale, Università di Napoli “Federico II”, Napoli, Italy (M.V., T.I.)
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Abstract

Phytocannabinoids modulate inflammatory responses by regulating the production of cytokines in several experimental models of inflammation. Cannabinoid type-2 (CB2) receptor activation was shown to reduce the production of the monocyte chemotactic protein-2 (MCP-2) chemokine in polyinosinic-polycytidylic acid [poly-(I:C)]–stimulated human keratinocyte (HaCaT) cells, an in vitro model of allergic contact dermatitis (ACD). We investigated if nonpsychotropic cannabinoids, such as cannabidiol (CBD), produced similar effects in this experimental model of ACD. HaCaT cells were stimulated with poly-(I:C), and the release of chemokines and cytokines was measured in the presence of CBD or other phytocannabinoids (such as cannabidiol acid, cannabidivarin, cannabidivarinic acid, cannabichromene, cannabigerol, cannabigerolic acid, cannabigevarin, tetrahydrocannabivarin, and tetrahydrocannabivarinic acid) and antagonists of CB1, CB2, or transient receptor potential vanilloid type-1 (TRPV1) receptors. HaCaT cell viability following phytocannabinoid treatment was also measured. The cellular levels of endocannabinoids [anandamide (AEA), 2-arachidonoylglycerol] and related molecules (palmitoylethanolamide, oleoylethanolamide) were quantified in poly-(I:C)–stimulated HaCaT cells treated with CBD. We show that in poly-(I:C)–stimulated HaCaT cells, CBD elevates the levels of AEA and dose-dependently inhibits poly-(I:C)–induced release of MCP-2, interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α in a manner reversed by CB2 and TRPV1 antagonists 6-iodopravadoline (AM630) and 5′-iodio-resiniferatoxin (I-RTX), respectively, with no cytotoxic effect. This is the first demonstration of the anti-inflammatory properties of CBD in an experimental model of ACD.

Footnotes

    • Received July 29, 2017.
    • Accepted March 6, 2018.
  • This work was partly supported by a research grant from GW Research Ltd to V.D.

  • S.P. and M.A. are employees of Epitech Group SpA. V.D. is the recipient of research grants, provides consultancy services, and performs sponsored research for GW Research Ltd. No other authors have conflicts of interests.

  • https://doi.org/10.1124/jpet.117.244368.

  • Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 365 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 365, Issue 3
1 Jun 2018
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Research ArticleInflammation, Immunopharmacology, and Asthma

Cannabidiol and Allergic Contact Dermatitis

Stefania Petrosino, Roberta Verde, Massimo Vaia, Marco Allarà, Teresa Iuvone and Vincenzo Di Marzo
Journal of Pharmacology and Experimental Therapeutics June 1, 2018, 365 (3) 652-663; DOI: https://doi.org/10.1124/jpet.117.244368

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Research ArticleInflammation, Immunopharmacology, and Asthma

Cannabidiol and Allergic Contact Dermatitis

Stefania Petrosino, Roberta Verde, Massimo Vaia, Marco Allarà, Teresa Iuvone and Vincenzo Di Marzo
Journal of Pharmacology and Experimental Therapeutics June 1, 2018, 365 (3) 652-663; DOI: https://doi.org/10.1124/jpet.117.244368
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