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Cannabinoid receptor double knockout mice (Cnr1 -/- /Cnr2 -/-) in CHS model

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. Keywords: Strain (Wt versus Ko) and disease state (DNFB treated versus control).

ORGANISM(S): Mus musculus

PROVIDER: GSE7694 | GEO | 2007/06/11

SECONDARY ACCESSION(S): PRJNA99455

REPOSITORIES: GEO

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

Project description: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.

2009-04-23 | E-GEOD-7694 | biostudies-arrayexpress

E-GEOD-7694

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

2014-07-29 | E-GEOD-7694 | ExpressionAtlas

RNA sequencing in the skin of non-responders and allergic individuals exposed to p-phenylenediamine

Project description:p-Phenylenediamine (PPD) is a strong contact allergen used in hair dye that is known to cause allergic contact dermatitis (ACD). We investigated the effects of PPD exposure on the skin of occupationally exposed subjects with and without clinical symptoms.

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Reactive oxygen species induced gene expression changes on dendritic cells

Project description:Identification of ROS induced genes on dendritic cells Dendritic cells were incubated for 15 min with or without a ROS inhibitor (DPI), washed extensively and incubated for 30 min with a chemical allergen (DNFB), hydrogen peroxide, and vehicle alone in HBSS containing DPI or vehicle. After washed extensively, the samples were post-incubated for 5.5 h with DNFB, hydrogen peroxide, or vehicle in complete culture medium containing DPI or vehicle. Total RNA was extracted from cells treated with a chemical allergen, hydrogen peroxide, and vehicle alone in the presence or absence of a ROS inhibitor.

2011-03-10 | E-GEOD-20727 | biostudies-arrayexpress

Cannabinoid Receptor 1 Dependent Effects of Isopropoyl dodeycl fluorophosphonate on Hepatic Gene Expression

Project description:We tested the effects of isopropoyl dodecyl fluorophosphonate (IDFP) (10 mg/kg, i.p.), a pharmacological inhibitor of endocannabinoid degradation, on hepatic gene expression in mice. To determine if increased cannabinoid receptor 1 signaling is responsible for IDFP induced effects a subset of mice were pretreated with the cannabinoid receptor 1 antagonist (AM251) (10 mg/kg, i.p.). Total RNA obtained from liver of mice treated with DMSO (n=6), IDFP (n=8), or AM251/IDFP (n=5) (all 10 mg/kg i.p.) for 4 hours.

2011-09-30 | E-GEOD-22949 | biostudies-arrayexpress

Chemical allergen-induced perturbations of the mouse lymph node DNA methylome

Project description:Epigenetic regulation of gene expression plays a pivotal role in the orchestration of immune responses and may determine the vigor, quality, or longevity of such responses. Chemical allergens can be divided into two categories: skin sensitizing chemicals associated with allergic contact dermatitis, and chemicals that cause sensitization of the respiratory tract and occupational asthma. In mice these are characterized by different T helper (Th) cell responses. To explore the regulation and maintenance of these divergent responses, mice were exposed to 2,4-dinitrochlorobenzene (DNCB; a contact allergen) or trimellitic anhydride (TMA; a respiratory allergen). DNA from draining lymph nodes was processed for methylated DNA immunoprecipitation (MeDIP) followed by hybridization to a whole-genome DNA promoter array. 6319 differently methylated regions (DMR) were identified following DNCB treatment, while 2178 DMRs were measured following TMA treatment, with approximately half of the TMA DMR common to DNCB. When limited to promoter region-associated DMR, 637 genes were uniquely associated with DNCB induced DMR but only 164 genes were unique to TMA DMR. Promoter-associated DMR unique to either DNCB or TMA were generally hypomethylated whereas DMR common to both allergens tended to be hypermethylated. Pathway analyses highlighted a number of immune related pathways, including chemokine and cytokine signalling. These data demonstrate that chemical allergen exposure results in characteristic patterns of DNA methylation indicative of epigenetic regulation of the allergic response. Comparison of methylation profiles from allergens 2,4-dinitrochlorobenzene (DNCB; a contact allergen) and trimellitic anhydride (TMA; a respiratory allergen) or vehicle acetone:olive oil (AOO).

2014-02-07 | E-GEOD-54768 | biostudies-arrayexpress

Cannabinoid Receptor 1 Dependent Effects of Isopropoyl dodeycl fluorophosphonate on Hepatic Gene Expression

2011-10-01 | GSE22949 | GEO

: The effects of chronic morphine on the endogenous cannabinoid system in the ventral tegmental area

Project description:The United States is currently facing a severe opioid epidemic, therefore addressing how opioids induce rewarding behaviors could be key to a solution for this medical and societal crisis. Recently, the endogenous cannabinoid system has emerged as a hot topic in the study of opioid reward but relatively little is known about how chronic opioid exposure may affect this system. In the present study, we investigated how chronic morphine may modulate the endogenous cannabinoid system in the ventral tegmental area (VTA), a critical region in the mesolimbic reward circuitry. Our studies found that the VTA expresses 32 different proteins or genes related to the endogenous cannabinoid system; 3 of these proteins or genes were significantly affected after chronic morphine exposure. We also investigated the effects of acute and chronic morphine treatment on the production of the primary endocannabinoids, 2-Arachidonoylglycerol (2-AG) and anandamide (AEA), and identified that acute, but not chronic, morphine treatment significantly reduced AEA production in the VTA; 2-AG levels were unchanged in either condition. Lastly, our studies exhibited a systemic enhancement of 2-AG tone via inhibition of monoacylglycerol lipase (MAGL)-mediated degradation and the pharmacological activation of cannabinoid receptor 2 (CB2R) significantly suppressed chronic morphine-induced conditioned place preference. Taken together, our studies offer a broad picture of chronic morphine-induced alterations of the VTA endogenous cannabinoid system, provide several uncharacterized targets that could be used to develop novel therapies, and identify how manipulation of the endocannabinoid system can mitigate opioid reward to directly address the ongoing opioid epidemic.

2021-04-08 | PXD023096 | Pride

Analysis of expression changes between IL-33 Knock out and WT mice in skin chronic inflammation

Project description:To find differential expression gene between IL-33KO and WT mice, we collected skin epithelial RNA sample after all of mice were treated with DNFB for 22 days. (allergen treat) After RNA-seq analysis, we got 203 genes which showed different expression level between IL-33KO and WT mice after allergen treated.

2021-01-28 | GSE149578 | GEO

Effect of Intradermal Immunotherapy (IDIT) injections on gene expression profiles of activated T cells derived from skin biopsy explants

Project description:A Randomized, Placebo-Controlled Trial of Intradermal Allergen Immunotherapy for Grass Pollen Allergy Background: Repeated intradermal injection of grass pollen (nanograms of allergen) suppresses allergen-induced cutaneous late phase responses, in keeping with effects of conventional high dose subcutaneous and sublingual immunotherapy. We evaluated the efficacy and safety of grass pollen intradermal immunotherapy for treatment of allergic rhinitis.Methods: We randomly assigned 93 adults with grass pollen allergic rhinitis to receive 7 pre-seasonal Intradermal allergen immunotherapy injections (containing 7 ng of Phl p 5 major allergen) or histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season. Skin biopsies were taken after the pollen season following an intradermal allergen challenge. Cutaneous late phase responses were measured 4 and either 7, 10 or 13 months post-treatment. Results No difference in the primary endpoint was observed between treatment arms (median difference, 14; 95% confidence interval [CI], -172.5 to 215.1; P=0.80). Amongst secondary endpoints, nasal symptoms measured with daily scores (median difference, 35; 95% CI, 4.0 to 67.5; P=0.03) and visual-analogue scales (median difference, 53; 95% CI, -11.6 to 125.2; P=0.05) were higher in the intradermal treatment group. Intradermal immunotherapy increased serum Phl p-specific IgE (P=0.001) compared to the control arm and T cells cultured from biopsies showed higher and lower surface of surface markers for Type 2 (P=0.04) and Type 1 (P=0.01) T-helper cells, respectively, Interleukin-5 was differentially expressed by microarray (P=0.03). Late phase responses were still inhibited 7 months after treatment (P=0.03) but not at 10-13 months. Conclusions Grass pollen intradermal allergen immunotherapy was not clinically effective but resulted in immunological priming and worsening of allergic rhinitis symptoms.

2017-06-23 | GSE72324 | GEO

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