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UBC Theses and Dissertations

Establishing the functional role of ORMDL3 in innate immunity Hsu, Karolynn Jo


Asthma and allergic diseases are rapidly becoming the most common chronic diseases in the developed world. Nearly 1 in 3 Canadians suffer from some form of allergy and more than 300 million individuals in the developed world suffer from asthma. These complex disorders are caused by the interaction of various genetic and environmental factors. Genome-wide association studies have been widely used to identify genes associated with asthma susceptibility. The gene, ORMDL3, was shown to be associated with early-onset asthma. Asthmatic patients have elevated expression levels of this gene. The gene encodes a transmembrane protein localized in the endoplasmic reticulum (ER) that may be involved in ER stress and inflammation. Its functional role in asthma pathogenesis, however, has yet to be elucidated. In this research, we investigated the functional role of ORMDL3 in innate immunity. Experimentally, ORMDL3 expression levels were manipulated in vitro in airway cells using overexpression plasmid and siRNA technologies. The effects of ORMDL3 expression levels on inflammatory responses were then explored. After manipulation of ORMDL3 expression levels, cells were stimulated with various immune response-inducing factors. Supernatants collected after stimulation were analyzed and no differences in proinflammatory cytokine production were observed. These results suggest that variation in ORMDL3 expression levels does not affect innate immune production of IL-6 and IL-8 in airway cells. ORMDL3 knockdown also did not affect expression of other immune-related genes.

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