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Chemokines in the Pathogenesis of Asthma (Asthma Chemokines)
EPA Grant Number: R826710C002Subproject: this is subproject number 002 , established and managed by the Center Director under grant R826710
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Michigan Center for the Environment and Children’s Health
Center Director: Israel, Barbara A.
Title: Chemokines in the Pathogenesis of Asthma (Asthma Chemokines)
Investigators: Israel, Barbara A. , Remick, Daniel
Current Investigators: Israel, Barbara A. , Brown, Randall , Keeler, Gerald J. , Lin, Xihong , Parker, Edith , Philbert, Martin , Remick, Daniel , Robins, Thomas
Institution: University of Michigan - Ann Arbor
EPA Project Officer: Saint, Chris
Project Period: January 1, 1998 through January 1, 2002
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998)
Research Category: Children's Health , Health Effects
Description:
Objective:Asthma represents a serious health problem particularly for inner city children. Recent studies have identified that many of the asthmatic attacks are triggered by exposure to cockroaches. It is not exposure to the entire cockroach, but only small fragments or residue. These small fragments are responsible for the allergic response and they are called allergens. In the normal allergic, or asthmatic response, the body reacts to the allergens to start inflammation. This inflammation is initiated by having the cells of the body produce specific chemicals or mediators. With asthma, most of the mediators are produced directly in the lung. While many potential mediators have been examined previously, asthma still exacts a toll on children and adults. More specific, targeted therapy has the potential to improve the treatment of asthma by identifying those mediators directly responsible for the causing disease. This research project will test the hypothesis that asthma-like pulmonary injury is mediated by the local production of specific mediators which are called chemokines. Chemokines are small molecular weight proteins which induce the movement and recruitment of inflammatory cells. The chemokines are powerful mediators with long lasting and potent biological activities. The first specific aim is to determine the acute and chronic pulmonary inflammation that develops after direct injection of the chemokines into the lung. The assessment of the injury will include a microscopic analysis of the lung as well as an assessment of the nerves within the airways. The second specific aim is to develop a mouse model of asthma-like pulmonary inflammation in response to cockroach allergens. For this specific aim a model in mice which is similar to humans will be set up to attempt to decipher the specific mediators that cause the lung injury. This model will be established by locating households with high levels of cockroach allergens and using this material to immunize the mice. The mice will be challenged by exposure to aerosols containing the dust with the cockroach allergens and the pulmonary injury carefully quantitated including an analysis of innervation of the airways. The third specific aim is to investigate the signals responsible for inducing the cells to make the chemokines. This will be done in cells sensitized and then challenged with cockroach allergens. This will focus on reactive oxygen and reactive nitrogen intermediates since they have been demonstrated to increase the synthesis of chemokines. The last specific aim is to rigorously test the central hypothesis that chemokines are important in causing asthma. This will be tested by blocking the biological activity of the chemokines with specific therapies to inhibit the chemokines and then determining if there is a reduction in the pulmonary inflammation induced by repeated exposures to the cockroach allergens. Successful completion of this project will both delineate the underlying mechanisms of disease and identify potential novel targets for intervention. Publications and Presentations:
Publications have been submitted on this subproject: View all 3 publications for this subproject | View all 46 publications for this center
Journal Articles:Journal Articles have been submitted on this subproject: View all 1 journal articles for this subproject | View all 26 journal articles for this center
Supplemental Keywords:children, health, asthma, exposure, home, indoor air, inner city, cockroach, chemokines, allergen. , Air, Scientific Discipline, Health, RFA, Susceptibility/Sensitive Population/Genetic Susceptibility, Toxicology, Biology, indoor air, genetic susceptability, Health Risk Assessment, Children's Health, Environmental Chemistry, Allergens/Asthma, environmental hazard exposures, allergen, health effects, indoor air quality, inhalation, respiratory problems, indoor environment, assessment of exposure, childhood respiratory disease, toxics, cockroaches, home, respiratory, sensitive populations, biological response, mediators, asthma chemokines, airway disease, children, lung, disease, exposure, pulmonary, children's vulnerablity, asthma triggers, allergic response, asthma, Human Health Risk Assessment, airway inflammation
Progress and Final Reports:
1999 Progress Report
2000 Progress Report
2002 Progress Report
Main Center Abstract and Reports:
R826710 Michigan Center for the Environment and Children’s Health
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R826710C001 Indoor and Outdoor Air Contaminant Exposures and Asthma Aggravation Among Children (Asthma Exposure)
R826710C002 Chemokines in the Pathogenesis of Asthma (Asthma Chemokines)
R826710C003 A Community-Based Intervention to Reduce Environmental Triggers for Asthma Among Children (Asthma Intervention)