Dissecting the Diet-Asthma Relationship in Mice Models of AsthmaEPA Grant Number: R834510C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R834510
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Mechanisms of Asthma-Dietary Interventions against Environmental Triggers - Johns Hopkins University
Center Director: Diette, Greg
Title: Dissecting the Diet-Asthma Relationship in Mice Models of Asthma
Investigators: Diette, Greg
Institution: The Johns Hopkins University
EPA Project Officer: Louie, Nica
Project Period: August 1, 2009 through July 31, 2014
RFA: Children's Environmental Health and Disease Prevention Research Centers (with NIEHS) (2009) RFA Text | Recipients Lists
Research Category: Children's Health , Health
The origination and development of asthma is a complex problem where environmental factors determine susceptibility. It can be 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 worsen preexisting airway inflammation leading to increased airway hyper-responsiveness, where the airways in the lungs narrow, making it difficult to breathe. The pollutants may also augment or modify the response of the immune system to inhaled antigens or intensify the effect of other pollutants in the respiratory system. Recent epidemiological studies revealed that diet is also a major risk factor in the pathogenesis (origin and development) of asthma. Most recently, dietary factors have been linked to poorer asthma health, pointing to a potential role for diet in perpetuating asthma disease. 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 mouse model of asthma similar to the dietary modifications being proposed in Project 2. The aims of Project 3 are: SA (Specific Aim) #1: To determine the effect of diet (proposed in Project 2-children intervention studies) on ovalbumin- (OVA) and ambient particle-induced-asthma in mouse 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 (an omega-3 fatty acid), high DHA and a high fat diet. SA #2: We will study asthma susceptibility by measuring different endpoints such as pulmonary inflammation, Th2 (T-helper cell type 2) cytokines (a measure of inflammation), and airway hyper-responsiveness. To study the regulation of Nrf2 pathway and its downstream antioxidant gene activation due to Sulforaphane, an antioxidant found in broccoli sprouts and other cruciferous vegetables such as cauliflower and cabbage, we will use Nrf2 +/+ and -/- mice to dissect the mechanism. SA #3: We will determine the effect of dietary constituents on dentritic cell (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.
Supplemental Keywords:air, ambient air, indoor air, exposure, risk, health effects, human health, metabolism, vulnerability, sensitive populations, animal, population, children, race, diet, sex, ethnic groups, susceptibility, particulates, nitrogen oxides, community-based, observation, engineering, epidemiology, biology, monitoring, measurement methods, Mid-Atlantic, Maryland, MD, Health, Scientific Discipline, Health Risk Assessment, Allergens/Asthma, Biology, asthma triggers, asthma indices, airway inflammation, air pollution, children, diet, oxidant stress
Progress and Final Reports:
Main Center Abstract and Reports:R834510 Mechanisms of Asthma-Dietary Interventions against Environmental Triggers - Johns Hopkins University
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834510C001 Urban Dietary Effects on the Asthmatic Response to Pollutants
R834510C002 Dietary Interventions in Asthma Treatment
R834510C003 Dissecting the Diet-Asthma Relationship in Mice Models of Asthma