Project 3: Dissecting the Diet Asthma Relationship in Mice Models of Asthma

Johns Hopkins University, Baltimore MD

Investigators

Linked publications & trials

Abstract

The pathogenesis of asthma is a complex problem where environmental factors determine susceptibility. It is often triggered in children by allergens (from rodents, pets, dust mites and plant pollens) and irritants, especially cigarette smoke and other indoor and outdoor air pollutants. Air pollutants can exacerbate preexisting airway inflammation leading to increased airway hyper-responsiveness. The pollutants may also augment or modify immune responses to inhaled antigens or intensify the effect of other pollutants in the respiratory tract. Recent epidemiological studies revealed that diet is also a major risk factor in the pathogenesis of asthma. Most recently, dietary factors have been linked to poorer asthma health, pointing to a potential role for diet in perpetuating asthma morbidity. Insufficient intake of vitamins and other dietary nutrients during pregnancy, for example, have been associated with a greater risk of development of asthma and wheezing symptoms in children. The "Western-style" diet, high in animal fats, junk food and sugary drinks has been associated asthma attacks and a "Mediterranean-style" diet rich in omega-3 containing fats and antioxidant containing foods such as whole fruits and vegetables has been shown to be protective. This ASTHMA-DIET Program will focus on investigating diet-asthma relationships and mechanisms in a mice model of asthma similar to the dietary modifications being proposed in Project 2. The aims of Project 3 are: SA#1: To determine the effect of dietary constituents (proposed in Project 2-children intervention studies) on OVA and ambient particle induced-asthma in mice models. The mice will be fed either a normal diet or a modified Mediterranean-type diet from which we will compare diets with low DHA, high DHA and a high fat diet. SA#2: We will study asthma susceptibility by measuring different endpoints such as pulmonary inflammation, Th2 cytokines, and airway hyper-responsiveness. To study the regulation of Nrf2 pathway and its downstream antioxidant gene activation due to Sulforaphane, we will use Nrf2 [+/+] and [-/-] mice to dissect the mechanism. SA#3: We will determine the effect of dietary constituents on DC maturation and Th2 polarization in the OVA and the ambient particle model of asthma. The proposed studies will help illustrate the mechanism by which diet modulates susceptibility and asthma pathogenesis.