|
| Status |
Public on Jun 20, 2014 |
| Title |
The role of Ch25h in the macrophage response to poly(I:C) (bone-marrow-derived macrophages) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Cross-talk between sterol regulatory pathways and inflammatory pathways has been demonstrated to play an important role in the response to viral infections. 25-Hydroxycholesterol (25HC) is an oxysterol that plays multiple roles in lipid biosynthesis and immunity, and has recently been shown to have anti-viral activity. Surprisingly, we found that deletion of Ch25h, the gene encoding the enzyme responsible for 25HC production, is protective in a mouse model of influenza infection as a result of decreased inflammatory-induced pathology. Anti-viral responses involve complex gene regulatory circuits with multiple feedback loops and we demonstrated that 25HC acts as an amplifier of TLR3 signaling in macrophages and airway epithelial cells.
We determined that 25HC amplifies TLR3 signaling, at least in part, by mediating the up-regulation and recruitment of the AP1 components Fos and Jun to the promoters of a subset of TLR3 responsive genes. Thus, our study demonstrates for the first time that in addition to its direct anti-viral role, 25HC also regulates transcriptional responses and acts as an amplifier of TLR3-induced inflammation via AP1.
|
| |
|
| Overall design |
24 RNA samples from murine bone-marrow-derived macrophages were analyzed using Agilent microarrays. Macrophages from C57BL/6 and Ch25h-/- mice were analyzed after mock stimulation or stimulation with 6ug/mL poly(I:C) or for 6 or 18 hours. For each condition, three biological replicates (macrophages derived from independent mice) were analyzed.
|
| |
|
| Contributor(s) |
Gold ES, Aderem A |
| Citation(s) |
24994901 |
| |
| Submission date |
Jan 14, 2014 |
| Last update date |
Jul 19, 2017 |
| Contact name |
Aderem Lab |
| E-mail(s) |
alan.diercks@seattlechildrens.org
|
| Organization name |
Seattle Children's Research Institute
|
| Lab |
Aderem Lab
|
| Street address |
307 Westlake Avenue North, Suite 500
|
| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
|
| Samples (24)
|
|
| This SubSeries is part of SuperSeries: |
| GSE54064 |
The role of Ch25h in the macrophage response to poly(I:C) |
|
| Relations |
| BioProject |
PRJNA234506 |
Less...
More...