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Series GSE54063 Query DataSets for GSE54063
Status Public on Jun 20, 2014
Title The role of Ch25h in the macrophage response to poly(I:C) (Let1a)
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 14 RNA samples from murine Let1a cells (immortalized airway epithelial cells) were analyzed using Agilent microarrays. Cells from C57BL/6 and Ch25h-/- mice were analyzed after mock stimulation or stimulation with 6ug/mL poly(I:C) or 5μM 25-Hydroxycholesterol for 6 or 18 hours. For each condition, two biological replicates 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 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 (14)
GSM1306617 Let1_Bl6_nostim.1
GSM1306618 Let1_Bl6_nostim.2
GSM1306619 Let1_Bl6_PIC6h.1
This SubSeries is part of SuperSeries:
GSE54064 The role of Ch25h in the macrophage response to poly(I:C)
Relations
BioProject PRJNA234507

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE54063_RAW.tar 173.9 Mb (http)(custom) TAR (of TXT)
Raw data provided as supplementary file
Processed data included within Sample table

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