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Regulation of Pattern Recognition Receptors by the Apolipoprotein A-I Mimetic Peptide 4F


ABSTRACT: The apolipoprotein A-I (apoA-I) mimetic peptide 4F displays prominent anti-inflammatory properties, including the ability to reduce vascular macrophage content. Macrophages are a heterogenous group of cells, represented by two principal phenotypes, the classically activated M1 macrophage and an alternatively activated M2 phenotype. We recently reported that 4F favors the differentiation of human monocytes to an anti-inflammatory phenotype similar to that displayed by M2 macrophages. In the current study, microarray analysis of gene expression in monocyte-derived macrophages (MDMs) was carried out to identify inflammatory pathways modulated by 4F treatment. ApoA-I treatment of MDMs served as a control. Transcriptional profiling revealed that 4F and apoA-I modulated expression of 113 and 135 genes that regulate inflammatory responses, respectively. Cluster heat maps revealed that 4F and apoA-I induced similar changes in expression for 69 common genes. Modulation of other gene products, including STAT1 and PPARG, were unique for 4F treatment. Besides modulating inflammatory responses, 4F was found to alter gene expression in cell-to-cell signaling, cell growth/proliferation, lipid metabolism and cardiovascular system development. These data suggest that the protective effects of 4F in a number of disease states may be due to underlying changes in monocyte/macrophage gene expression. 16 samples analyzed (four 4F+LPS, four 4F, four Controls+LPS, four Controls).

ORGANISM(S): Homo sapiens

SUBMITTER: Geeta Datta 

PROVIDER: E-GEOD-36933 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Regulation of pattern recognition receptors by the apolipoprotein A-I mimetic peptide 4F.

White C Roger CR   Smythies Lesley E LE   Crossman David K DK   Palgunachari Mayakonda N MN   Anantharamaiah G M GM   Datta Geeta G  

Arteriosclerosis, thrombosis, and vascular biology 20120913 11


<h4>Objective</h4>The apolipoprotein A-I (apoA-I) mimetic peptide 4F favors the differentiation of human monocytes to an anti-inflammatory phenotype and attenuates lipopolysaccharide (LPS)-induced inflammatory responses. We investigated the effects of LPS on the Toll-like receptor (TLR) signaling pathway in 4F-differentiated monocyte-derived macrophages.<h4>Methods and results</h4>Monocyte-derived macrophages were pretreated with 4F or vehicle for 7 days. 4F downregulated cell-surface TLRs (4, 5  ...[more]

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