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Status |
Public on Oct 01, 2010 |
Title |
HDL suppresses the type I interferon response |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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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.
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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).
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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
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Organization name |
University of Washington
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Department |
Environmental and Occupational Health Sciences
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Street address |
4225 Roosevelt Way NE
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City |
Seattle |
State/province |
WA |
ZIP/Postal code |
98105-6099 |
Country |
USA |
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Platforms (1) |
GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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Samples (12)
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Relations |
BioProject |
PRJNA121713 |
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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