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Series GSE19340 Query DataSets for GSE19340
Status Public on Oct 01, 2010
Title HDL suppresses the type I interferon response
Organism Mus musculus
Experiment type Expression profiling by array
Summary Background: High density lipoprotein (HDL) protects the artery wall by removing cholesterol from lipid-laden macrophages. However, recent evidence suggests that it might also inhibit atherogenesis by combating inflammation. Methods and Results: To identify potential anti-inflammatory mechanisms, we challenged macrophages with lipopolysaccharide (LPS), an inflammatory microbial ligand for Toll-like receptor 4 (TLR4). HDL inhibited the expression of 33% (301 of 911) of the genes normally induced by LPS, microarray analysis revealed. One of its major targets was the type I interferon response pathway, a family of potent viral immunoregulators controlled by TLR4 and the TRAM/TRIF signaling pathway. Unexpectedly, HDL’s ability to inhibit gene expression was independent of cellular cholesterol stores. Moreover, it was unaffected by downregulation of two ATP-binding cassette transporters, ABCA1 and ABCG1, that promote cholesterol efflux. To examine the pathway’s potential in vivo relevance, we used mice deficient in apolipoprotein (apo) A-I, HDL’s major protein. After infection with Salmonella (a Gram-negative bacterium that expresses LPS), apoA-I–deficient mice had 6-fold higher plasma levels of interferon-beta-a key regulator of the type I interferon response than did wild-type mice. Conclusions: HDL inhibits a subset of LPS-stimulated macrophage genes that regulate the type I interferon response, and its action is independent of sterol metabolism. These findings raise the possibility that regulation of macrophage genes by HDL might link innate immunity and cardioprotection.
 
Overall design 12 arrays, 3 experimental groups, mMncN (no treatment), mMncL (LPS treated, exposed for 4 h to serum-free medium or serum-free medium supplemented with 100 ng/mL of LPS), and mMwtL (HDL treated, Macrophages were treated for 4 h with serum-free medium or serum-free medium supplemented with 50 mg/mL of HDL, washed twice with PBS).
 
Contributor(s) Beyer RP, Suzuki M, Pritchard DK, Becker L, Hoofnagle AN, Bammler TK, Bumgarner R, Vaisar T, de Beer MC, de Beer FC, Oram JF, Heinecke JW
Citation(s) 20974999
Submission date Dec 05, 2009
Last update date Mar 04, 2019
Contact name James William MacDonald
E-mail(s) jmacdon@uw.edu
Organization name University of Washington
Department Environmental and Occupational Health Sciences
Street address 4225 Roosevelt Way NE
City Seattle
State/province WA
ZIP/Postal code 98105-6099
Country USA
 
Platforms (1)
GPL6246 [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]
Samples (12)
GSM480390 25A-1_mMncN1_482JH
GSM480391 26A-1_mMncN2_482JH
GSM480392 27A-1_mMncN3_482JH
Relations
BioProject PRJNA121713

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
GSE19340_RAW.tar 49.6 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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