Attenuation of allergic contact dermatitis through the endocannabinoid system.
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.
Karsak
Meliha
M
Department of Molecular Psychiatry, University of Bonn, Germany.
Gaffal
Evelyn
E
Date
Rahul
R
Wang-Eckhardt
Lihua
L
Rehnelt
Jennifer
J
Petrosino
Stefania
S
Starowicz
Katarzyna
K
Steuder
Regina
R
Schlicker
Eberhard
E
Cravatt
Benjamin
B
Mechoulam
Raphael
R
Buettner
Reinhard
R
Werner
Sabine
S
Di Marzo
Vincenzo
V
Tüting
Thomas
T
Zimmer
Andreas
A
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001892:Camphanes / Q000008:administration & dosage / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology; D018925:Chemokines / Q000502:physiology; D017449:Dermatitis, Allergic Contact / Q000473:pathology / Q000503:physiopathology*; D004139:Dinitrofluorobenzene; D004195:Disease Models, Animal; D015536:Down-Regulation; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology; D063388:Endocannabinoids; D005260:Female; D005989:Glycerides / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000077285:Rimonabant; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D001095:Arachidonic Acids; D001892:Camphanes; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D018925:Chemokines; D063388:Endocannabinoids; D005989:Glycerides; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; D013759:Dronabinol; C094503:glyceryl 2-arachidonate; C402416:HU 308; D004139:Dinitrofluorobenzene; D000077285:Rimonabant; C078814:anandamide