Effects of Insulin and Glucose Stimulation on the Anti-Viral Response in Bronchial Epithelial Cells

Sammanfattning: Asthma exacerbation is among the leading causes of mortality and morbidity. Bronchial epithelial cells (BECs) are of interest because they represent not only a physical barrier against infections, but also a biological barrier between the inhaled agents, such as allergens, and the immune system. As known, systemic inflammation of the lungs, or dietary factors could have effects on lung disease worsening. Metabolic syndrome is another crucial medical condition that exhibits high levels of glucose (hyperglycaemia), systemic inflammation, obesity, as well as insulin resistance which is a risk factor for asthma development. Insulin resistance also links asthma with metabolic syndrome and obesity. Deficient production of anti-viral interferons (IFNs) may be involved in causing viral-induced asthma exacerbations. Allergens also a risk factor for viral-induced asthma exacerbation. Hence, drugs inducing lung IFN production would be warranted. In the current project, the effects of elevated levels of glucose and insulin on viral-induced IFNβ in BECs and in-vitro asthma exacerbation model have been investigated. Although our results are preliminary, we have showed that glucose and insulin might increase viral-induced IFNβ production in BECs and restored house dust mite (HDM)-impaired IFNβ expression in an in-vitro asthma exacerbation model. We assume that insulin effects are abrogated in the presence of insulin resistance conditions, which could be a risk factor for asthma exacerbation development in obese and diabetes asthmatics. We have shown that PRRs, including TLR-3, RIG-I, and MDA5, are not involved in the process of the enhancement of IFNβ by insulin and glucose actions.