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Status |
Public on Nov 10, 2010 |
Title |
Novel mediators of eicosanoid and epithelial nitric oxide production in asthma |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
|
Summary |
Asthma is a heterogeneous disease. Exercise-induced bronchoconstriction (EIB) is a distinct syndrome that occurs in 30-50% of asthmatics and is characterized by high levels of pro-inflammatory eicosanoids. We identified genes differentially expressed in the airways of asthmatics with EIB relative to asthmatics without EIB. Genes related to epithelial repair and mast cell infiltration including beta-tryptase and carboxypeptidase A3 were upregulated by exercise challenge in the asthma group with EIB. We confirmed that two novel mediators trefoil factor 3 (TFF3) and transglutaminase 2 (TGM2) have increased expression in airways cells and secreted product in the airways. In vitro studies indicate that 1) TFF3 induces nitric oxide synthase in airway epithelial cells from asthmatics and 2) TGM2 augments the enzymatic activity of secreted phospholipase A2 (sPLA2) group X, an enzyme recently been implicated in asthma pathogenesis. Since PLA2 serves as the first rate-limiting step leading to eicosanoid generation, these results suggest that TGM2 may be a key initiator of the airway inflammatory cascade in asthma.
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Overall design |
EIB positive and EIB negative subjects sampled pre- and post-exercise
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Contributor(s) |
Beyer RP, Hallstrand TS, Wurfel MM, Lai Y, Ni Z, Gelb MH, Altemeier WA, Aitken ML, Henderson WR |
Citation(s) |
20052409 |
|
Submission date |
Dec 01, 2008 |
Last update date |
Mar 25, 2019 |
Contact name |
James William MacDonald |
E-mail(s) |
[email protected]
|
Organization name |
University of Washington
|
Department |
Environmental and Occupational Health Sciences
|
Street address |
4225 Roosevelt Way NE
|
City |
Seattle |
State/province |
WA |
ZIP/Postal code |
98105-6099 |
Country |
USA |
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Platforms (2) |
GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
|
Samples (22)
|
GSM346858 |
Subject6_EIB_negative_pre_exercise |
GSM346859 |
Subject6_EIB_negative_post_exercise |
GSM346860 |
Subject7_EIB_positive_pre_exercise |
GSM346861 |
Subject7_EIB_positive_post_exercise |
GSM346862 |
Subject8_EIB_negative_pre_exercise |
GSM346863 |
Subject8_EIB_negative_post_exercise |
GSM346864 |
Subject9_EIB_positive_pre_exercise |
GSM346865 |
Subject9_EIB_positive_post_exercise |
GSM346866 |
Subject10_EIB_positive_pre_exercise |
GSM346867 |
Subject10_EIB_positive_post_exercise |
GSM346868 |
Subject11_EIB_negative_pre_exercise |
GSM346869 |
Subject11_EIB_negative_post_exercise |
GSM346988 |
Subject1_EIB_positive_pre_exercise |
GSM346989 |
Subject1_EIB_positive_post_exercise |
GSM346990 |
Subject2_EIB_positive_pre_exercise |
GSM346991 |
Subject2_EIB_positive_post_exercise |
GSM346992 |
Subject3_EIB_positive_pre_exercise |
GSM346993 |
Subject3_EIB_positive_post_exercise |
GSM346994 |
Subject4_EIB_negative_pre_exercise |
GSM346995 |
Subject4_EIB_negative_post_exercise |
GSM346996 |
Subject5_EIB_negative_pre_exercise |
GSM346997 |
Subject5_EIB_negative_post_exercise |
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Relations |
BioProject |
PRJNA110615 |