 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 01, 2013 |
| Title |
IL-33 markedly induces murine eosinophil gene transcription via autocrine IL-4-dependent and -independent mechanisms |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Eosinophils are major effector cells in type 2 inflammatory responses and become activated in response to IL-4 and IL-33, yet the molecular mechanism remains unclear. We examined the direct effect of these cytokines on eosinophils and demonstrated that murine eosinophils respond to IL-4 and IL-33 by phosphorylation of STAT-6 and NFkB, respectively. RNA sequencing analysis of murine eosinophils indicated that IL-33 regulates 519 genes, whereas IL-4 regulates only 28 genes, including 19 IL-33-regulated genes. Interestingly, IL-33 induced eosinophil activation via two distinct mechanisms, IL-4 independent and IL-4 secretion/auto-stimulation dependent. Anti-IL-4 or anti-IL-4Ra antibody-treated eosinophils, as well as Il4- or Stat6-deficient eosinophils, had attenuated protein secretion of a subset of IL-33-induced genes, including Retnla and Ccl17. However, the induction of most IL-33-regulated transcripts (e.g. Il6 and Il13) was IL-4 independent and blocked by NFkB inhibition. Indeed, IL-33 induced the rapid release of pre-formed IL-4 protein from eosinophils by an NFkB-dependent mechanism. Thus, we have identified a novel activation pathway in murine eosinophils that is induced by IL-33 and differentially dependent upon IL-4. These data suggest that IL-4 plays a critical role in auto-amplification of IL-33-induced eosinophil activation and could be a potential target for therapeutic approaches in IL-33-related eosinophil-associated diseases.
|
| |
|
| Overall design |
Low density bone marrow derived murine eosinophils were generated in culture over the period of 14 days. Eosinophils were activated by either IL-33 or IL-4 at 10 ng/ml for 1hr and 4hr. RNA was collected and subjected to next generation sequencing.
|
| |
|
| Contributor(s) |
Rothenberg ME |
| Citation(s) |
24043894 |
| Submission date |
Jan 22, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Mark Rochman |
| E-mail(s) |
mark.rochman@cchmc.org
|
| Phone |
5138038017
|
| Organization name |
CCHMC
|
| Department |
Allergy and Immunology
|
| Street address |
3333 Burnett Ave
|
| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45229 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA186948 |
| SRA |
SRP018093 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE43660_control_vs_IL4_1hr.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
| GSE43660_control_vs_IL4_4hr.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
| GSE43660_control_vs_il33_1hr.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
| GSE43660_control_vs_il33_4hr.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
| GSE43660_significantly_regulated_genes.txt.gz |
25.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...