The central hypothesis of this proposal is that epithelial cell shedding and death after allergen or environmental exposure occurs due to initiation of epithelial cell apoptosis.
In specific aim 1, the investigator will determine the expression of fas and fasL in fixed airway tissue from normal subjects and patients with asthma or other chronic pulmonary disease. He will also use primary and permanent airway epithelial cell lines to study the regulation of this expression by inflammatory cytokines expected to regulate fas expression and by metalloproteinases expected to regulate fasL expression. Additionally, the investigator will look at intracellular expression of proteins implicated in apoptotic signaling. Through these and other studies, it may be possible to establish a roles for fas and fasL in airway damage and to define the principal apoptotic pathways in human airway epithelium.
In specific aim 2, he will demonstrate roles for fas and related apoptosis receptors in airway epithelial shedding and death after allergen challenge in the mouse ovalbumin asthma model, and will determine if airway damage is altered in mice lacking fas or fas ligand or in normal mice treated with exogenous agonists/antagonists of fas.
In specific aim 3, the investigator will demonstrate roles for fas and related apoptosis receptors in epithelial shedding after allergen challenge in human airways and will study the ability of inhaled cortisone to decrease allergen-stimulated cell shedding and death.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL060531-04
Application #
6184507
Study Section
Special Emphasis Panel (ZES1-LKB-A (R1))
Project Start
1997-09-30
Project End
2001-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
4
Fiscal Year
2000
Total Cost
$233,749
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
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