Abstract
Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity, we show that mice lacking both known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase-deficient mice, which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid receptor antagonists exacerbated allergic inflammation, whereas receptor agonists attenuated inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin and suggest a target for therapeutic intervention.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arachidonic Acids / metabolism
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Camphanes / administration & dosage
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Camphanes / pharmacology
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Cannabinoid Receptor Modulators / physiology*
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Cannabinoids / administration & dosage
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Cannabinoids / pharmacology
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Chemokines / physiology
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Dermatitis, Allergic Contact / pathology
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Dermatitis, Allergic Contact / physiopathology*
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Dinitrofluorobenzene
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Disease Models, Animal
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Down-Regulation
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Dronabinol / administration & dosage
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Dronabinol / pharmacology
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Endocannabinoids*
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Female
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Glycerides / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Oligonucleotide Array Sequence Analysis
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Piperidines / administration & dosage
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Piperidines / pharmacology
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Polyunsaturated Alkamides / metabolism
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Pyrazoles / administration & dosage
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Pyrazoles / pharmacology
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Receptor, Cannabinoid, CB1 / agonists
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Receptor, Cannabinoid, CB1 / antagonists & inhibitors
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Receptor, Cannabinoid, CB1 / genetics
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Receptor, Cannabinoid, CB1 / physiology*
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Receptor, Cannabinoid, CB2 / agonists
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Receptor, Cannabinoid, CB2 / antagonists & inhibitors
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Receptor, Cannabinoid, CB2 / genetics
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Receptor, Cannabinoid, CB2 / physiology*
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Rimonabant
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Skin / metabolism*
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Skin / pathology
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Up-Regulation
Substances
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Arachidonic Acids
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Camphanes
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Cannabinoid Receptor Modulators
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Cannabinoids
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Chemokines
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Endocannabinoids
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Glycerides
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Piperidines
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Polyunsaturated Alkamides
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Pyrazoles
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Receptor, Cannabinoid, CB1
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Receptor, Cannabinoid, CB2
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SR 144528
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Dronabinol
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glyceryl 2-arachidonate
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HU 308
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Dinitrofluorobenzene
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Rimonabant
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anandamide