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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 06, 2009 |
| Title |
Gene expression profiling of experimental asthma reveals a possible role of paraoxonase-1 in asthma |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Background: Several studies indicate that asthma is a polygenic disease, and its complexity originates from the interaction of an unknown number of genes with environmental factors.
Objective: In this study we aimed to identify new genes, gene groups and pathways involved in the pathogenesis of experimental asthma.
Methods: In an ovalbumin-induced murine model of asthma we applied microarray gene expression analysis of the lung at different time points in the asthmatic process. Advanced statistical methods were used to relate gene expression changes to cellular processes and to integrate our results into multiple levels of information available in public databases.
Results: According to the observed marked neutrophil infiltration found early, at 4 hours after the first allergen challenge, gene expression pattern reflected mainly an acute inflammatory response and strong chemotactic activity. At 24 hours after the third allergen challenge, gene set enrichment analysis revealed significant overrepresentation of gene sets corresponding to Th2 type inflammation models. Among the top downregulated transcripts, an antioxidant enzyme, paraoxonase-1 (PON1) was identified. Reduced PON1 protein expression in the lung was confirmed by immunohistochemical analysis. In human asthmatic patients we found that serum PON1 activity was reduced at exacerbation, but increased parallel with improving asthma symptoms. PON1 gene polymorphisms did not influence the susceptibility to the disease.
Conclusion: Our observations suggest that an altered PON1 activity might be involved in the pathogenesis of asthma, and PON1 might be a potential new therapeutic target as well as a new diagnostic tool for following up the effect of therapy.
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| Overall design |
Experimental design:
Three groups of mice (6 mice/group) were sensitized and challenged with allergen (OVA), one group (control group) was sensitized and challenged with placebo (PBS) and served as a control. On day 28 and 30, 4 h after the first and third allergen challenge, mice in groups 1 and 2 were anaesthetized by an intraperitoneal injection of ketamine and xylazine, BAL was isolated and the lungs were removed for further analysis. On day 31, 24h after the third (last) allergen challenge mice in group 3 and the controls were anaesthetized, and airway hyper-responsiveness (AHR) was assessed. After the AHR measurements, BAL sampling and lung tissue collection were performed, the same way as it was carried out in groups 1 and 2. Cellular composition of BAL, and lung histology were examined in all mice in all groups. AHR was measured in controls and group 3 on day 31. 1000 ng-1000 ng quality-checked total lung tissue RNA samples from OVA sensitized and challenged mice from group 1, 2 and 3 were identically labeled with Cy5 dye, while lung tissue RNA samples from group 4 (control, placebo sensitized and challenged) were pooled and labeled with Cy3 dye, and served as a common reference.
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| Contributor(s) |
Tölgyesi G, Molnár V, Wiener Z, Komlósi ZI, Pócza P, Falus A, Losonczy G, Szalai C |
| Citation(s) |
19556304, 32180797 |
| Submission date |
Jun 27, 2008 |
| Last update date |
Mar 23, 2020 |
| Contact name |
Gergely Tolgyesi |
| E-mail(s) |
tolgyesi_gergely@yahoo.com
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| Organization name |
Semmelweis University Budapest
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| Street address |
Nagyvarad ter 4
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| City |
Budapest |
| ZIP/Postal code |
1089 |
| Country |
Hungary |
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| Platforms (1) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
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| Samples (12)
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| GSM301072 |
4 hrs after the first OVA challenge Lung tissue Group1_1 |
| GSM301080 |
4 hrs after the first OVA challenge Lung tissue_Group1_2 |
| GSM301082 |
4 hrs after the first OVA challenge Lung tissue Group1_4 |
| GSM301083 |
4 hrs after the first OVA challenge Lung tissue Group1_5 |
| GSM301084 |
4 hrs after the third OVA challenge Lung tissue Group2_1 |
| GSM301085 |
4 hrs after the third OVA challenge Lung tissue Group2_2 |
| GSM301086 |
4 hrs after the third OVA challenge Lung tissue Group2_3 |
| GSM301087 |
4 hrs after the third OVA challenge Lung tissue Group2_4 |
| GSM301088 |
24 hrs after the third OVA challenge Lung tissue Group3_2 |
| GSM301089 |
24 hrs after the third OVA challenge Lung tissue Group3_3 |
| GSM301090 |
24 hrs after the third OVA challenge Lung tissue Group3_4 |
| GSM301091 |
24 hrs after the third OVA challenge Lung tissue Group3_5 |
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| Relations |
| BioProject |
PRJNA105753 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE11911_RAW.tar |
6.6 Mb |
(http)(custom) |
TAR |
| Processed data included within Sample table |
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