Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse Cannabinoid receptor double knockouts (Cnr1 -/- /Cnr2 -/-) in CHS model to investigate cutaneous contact hypersensitivity

ABSTRACT: We evaluated cutaneous contact hypersensitivity (CHS) in Cnr1-/-/Cnr2-/- animals using the obligate contact allergen 2,4-dinitrofluorobenzene (DNFB), which generates a specific cutaneous T-cell mediated allergic response upon repeated allergen contact. 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 whereas receptor agonists attenuated allergic inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin, and suggest a novel target for therapeutic intervention. Experiment Overall Design: Three wildtype mice (Wt) and three Cnr1-/-/Cnr2-/- (Ko) mice were used. Contact hypersensitivity was determined always at the right ears, which therefore were treated with DNFB (Tr). Left ears of mice were kept untreated and served as control ears (C). A total of 12 hybridizations were performed (2 strains x 2 treatments X 3 biological replicates) in this experiment.

ORGANISM(S): Mus musculus

SUBMITTER: Meliha Karsak

PROVIDER: E-GEOD-7694 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Attenuation of allergic contact dermatitis through the endocannabinoid system.

Karsak Meliha M 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

Science (New York, N.Y.) 20070601 5830

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 r ...[more]

PMID: 17556587

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Project description:Spiral ganglion neurons (SGNs) and the associated components of the auditory nerve are primary carriers of auditory information from hair cells to the brain. Loss of SGNs occurs with many pathological conditions, resulting in permanent sensorineural hearing loss. Neural stem/progenitors (NSPs) have been well-characterized in several locations of adult brain and retina. However, it is unclear whether NSPs are present in the adult auditory nerve. Here we examined the self-renewal potential of the adult auditory nerve using ouabain application as a well-established mouse model of acute SGN injury. The observed increase in cell proliferation, alteration in enchromatin/heterochromatin ratio and down-regulation of histone deacetylase expression in glial cells suggest that the quiescent glial cells convert to an activated state after SGN degeneration. This was further confirmed by global gene expression analysis of injured auditory nerves, which showed up-regulation of numerous neurogenesis- and/or development-associated genes shortly after ouabain exposure. These genes include molecular markers commonly used for the identification of NSPs. Under a strict culture regimen, auditory nerve-derived cells of adult mouse ears gave rise to neurospheres, suggesting that multipotent NSPs are present in adult cochlear nerve. Neurosphere assays on Sox2 transgenic mice revealed that Sox2+ glial cells are the source for NSPs. Our data also showed that acute injury or hypoxia enhances neurosphere formation. Taken together, our study revealed that glial cells of adult cochlea exhibit several NSP characteristics, and hence these mature non-neuronal cells may be important targets for promoting self-repair of degenerative auditory nerves. Adult Mice (CBA/CaJ, aged 8 to 12 weeks) were anesthetized and subjected to survival surgery to expose the bulla of the right ear. A ouabain solution (3 mM, approximately 10 ul) was administered in the round window niche. This solution was wicked away and replaced with fresh ouabain approximately every 10 min during a cummulative exposure period of 60 min. The left ears (i.e., contralateral) were not surgically manipulated and were used as controls. Mice were maintained for 3 days or 7 days following treatments, then euthanized, and the oubain-treated and contralateral cochleas were removed. Cochleas underwent microdissection to remove the outer bony cochlear shell and cochlear lateral wall, thus preserving the modiolus portion of cochlea which contains mainly the auditory nerve. All sample types were prepared in experimental triplicate (n=3).

Dataset Information

Transcription profiling of mouse Cannabinoid receptor double knockouts (Cnr1 -/- /Cnr2 -/-) in CHS model to investigate cutaneous contact hypersensitivity

Publications

Attenuation of allergic contact dermatitis through the endocannabinoid system.

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