 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Oct 01, 2008 |
| Title |
Influence of CFTR on Lipid Metabolism Gene Expression in Marrow Derived Dendritic Cells infected with P. aeruginosa |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Dysfunction of the cystic fibrosis transmembrane regulator (CFTR) in cystic fibrosis (CF) results in exaggerated and chronic inflammation as well as increased susceptibility to chronic pulmonary infections, in particular with Pseudomonas aeruginosa. Based on the concept that host immune responses do not seem to be adequate to eradicate P.aeruginosa from the lungs of CF patients and that dendritic cells (DC) play an important role in initiating and shaping adaptive immune responses, this study analyzed the role of CFTR in bone marrow-derived murine DC from CFTR knockout (CF) mice with and without exposure to P.aeruginosa. DC expressed CFTR mRNA and protein, although at much lower levels compared to whole lung. Microarray analysis of gene expression levels in DC generated from CF and wild type (WT) mice revealed significantly different expression of 16 genes in CF DC compared to WT DC. Among the genes with lower expression in CF DC was Caveolin-1, a membrane lipid raft protein. Messenger RNA and protein levels of Caveolin-1 were decreased in the CF DC compared to WT DC. Consistently, the active form of sterol-responsive element binding protein (SREBP), a negative regulator of Caveolin-1 expression, was increased in CF DC. Following exposure to P.aeruginosa, gene expression levels in CF and WT DC changed for 912 genes involved in inflammation, chemotaxis, signaling, cell cycling and apoptosis more than 1.5-fold. Among the genes that showed a different response between WT and CF DC infected with P.aeruginosa, were 3β-hydroxysterol-Δ7 reductase (Dhcr7) and stearoyl-CoA desaturase 2 (Scd2), two enzymes involved in the lipid metabolism that are also regulated by SREBP. These results suggest that CFTR dysfunction in non-epithelial cells results in changes in the expression of genes encoding factors involved in membrane structure and lipid-metabolism. These membrane alterations in immune cells may contribute to the abnormal inflammatory and immune response characteristic of CF.
Keywords: CF control vs CF PAK vs WT control vs WT PAK
|
| |
|
| Overall design |
comparison of gene expression in dendritic cells of cystic fibrosis mice without or with Pseudosmonas aeruginosa infection vs wild type dendritic cell controls
|
| |
|
| Contributor(s) |
Xu Y, Tertilt C, Quadri L, Crystal RG, Worgall S |
| Citation(s) |
19344509 |
| Submission date |
Oct 31, 2007 |
| Last update date |
Feb 18, 2018 |
| Contact name |
Stefan Worgall |
| E-mail(s) |
stw2006@med.cornell.edu
|
| Phone |
212-746-4875
|
| Fax |
212-746-8261
|
| Organization name |
Weill Cornell Medical College
|
| Department |
Genetic Medicine
|
| Lab |
Worgall
|
| Street address |
515 East 71st Street
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL81 |
[MG_U74Av2] Affymetrix Murine Genome U74A Version 2 Array |
|
| Samples (24)
|
|
| Relations |
| BioProject |
PRJNA103271 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE9488_RAW.tar |
55.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...