Year of Award

2013

Document Type

Thesis

Degree Type

Master of Science (MS)

Degree Name

Toxicology

Department or School/College

Department of Biomedical and Pharmaceutical Sciences

Committee Chair

Kevan Roberts

Commitee Members

Christopher Migliaccio, Xi Chu

Keywords

ALLERGIC AIRWAY INFLAMMATION, ASTHMA, CANNABINOID RECEPTOR 2 (CB2) AGONIST, MOUSE

Publisher

University of Montana

Abstract

Allergic asthma is a chronic inflammatory disease that affects approximately 300 million people worldwide. The health problem is compounded by the fact that the prevalence of the disease is increasing in the Western world. Thus, there is a continued need for new and improved therapies for the disease. Recently, it has become evident that cannabinoids have immunosuppressive properties and can be used as therapeutics for various inflammatory diseases. The main aim of this study was to explore the anti-inflammatory effects of CB2 agonists on allergic airway inflammation using a mouse model of asthma and resolve any mechanisms that underpin the immunosuppressive properties observed using in vitro assays. The murine model of allergic lung inflammation entailed transferring ovalbumin (OVA) specific CD4+ T cells into normal BALB/c mice which then inhaled OVA for 7 days. Mice were treated daily with either CB2 compound or vehicle, and the anti-inflammatory effect of the CB2 agonist was examined by monitoring the effect of the treatment on the level of inflammation and histological changes. Intra-nasal administration of CB2 analog suppressed the development of a pulmonary eosinophilia and the recruitment of allergen-specific CD4+ T cells into the airways. To assist in resolving the mode of action of these compounds the expression of CB2 receptors on Th2 cells was examined using a novel NBD-labeled CB2-selective compound. In additional experiments, cells were cultured with CB2-selective agonist and the effect on Th2 cytokine production was determined. Our data suggest that the attenuation of inflammation mediated by CB2 agonists is associated with the reduction of pro-inflammatory cytokines and the induction of anti-inflammatory cytokine.

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© Copyright 2013 Soram Hong