Dataset Information


HDL suppresses the type I interferon response

ABSTRACT: 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. 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).

ORGANISM(S): Mus musculus  

SUBMITTER: Masashi Suzuki   Maria C de Beer  Lev Becker  Jay W Heinecke  Richard Beyer  Theo K Bammler  Richard P Beyer  Frederick C de Beer  John F Oram  Andrew N Hoofnagle  Tomas Vaisar  David K Pritchard  Roger Bumgarner 

PROVIDER: E-GEOD-19340 | ArrayExpress | 2010-10-01



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E-GEOD-19340.README.txt Txt
E-GEOD-19340.eSet.r Other
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