Dataset Information

Statins affect the presentation of endothelial chemokines by targeting to multivesicular bodies.

ABSTRACT:

Background

In addition to lowering cholesterol, statins are thought to beneficially modulate inflammation. Several chemokines including CXCL1/growth-related oncogene (GRO)-?, CXCL8/interleukin (IL)-8 and CCL2/monocyte chemoattractant protein (MCP)-1 are important in the pathogenesis of atherosclerosis and can be influenced by statin-treatment. Recently, we observed that atorvastatin-treatment alters the intracellular content and subcellular distribution of GRO-? in cultured human umbilical vein endothelial cells (HUVECs). The objective of this study was to investigate the mechanisms involved in this phenomenon.

Methodology/ principal findings

The effect of atorvastatin on secretion levels and subcellular distribution of GRO-?, IL-8 and MCP-1 in HUVECs activated by interleukin (IL)-1? were evaluated by ELISA, confocal microscopy and immunoelectron microscopy. Atorvastatin increased the intracellular contents of GRO-?, IL-8, and MCP-1 and induced colocalization with E-selectin in multivesicular bodies. This effect was prevented by adding the isoprenylation substrate GGPP, but not the cholesterol precursor squalene, indicating that atorvastatin exerts these effects by inhibiting isoprenylation rather than depleting the cells of cholesterol.

Conclusions/ significance

Atorvastatin targets inflammatory chemokines to the endocytic pathway and multivesicular bodies and may contribute to explain the anti-inflammatory effect of statins at the level of endothelial cell function.

SUBMITTER: Hol J

PROVIDER: S-EPMC3398041 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Statins affect the presentation of endothelial chemokines by targeting to multivesicular bodies.

Hol Johanna J Otterdal Kari K Breland Unni M UM Stang Espen E Pedersen Turid M TM Hagelsteen Kathrine K Ranheim Trine T Kasprzycka Monika M Halvorsen Bente B Haraldsen Guttorm G Aukrust Pål P

PloS one 20120716 7

<h4>Background</h4>In addition to lowering cholesterol, statins are thought to beneficially modulate inflammation. Several chemokines including CXCL1/growth-related oncogene (GRO)-α, CXCL8/interleukin (IL)-8 and CCL2/monocyte chemoattractant protein (MCP)-1 are important in the pathogenesis of atherosclerosis and can be influenced by statin-treatment. Recently, we observed that atorvastatin-treatment alters the intracellular content and subcellular distribution of GRO-α in cultured human umbilic ...[more]

PMID: 22815786

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Dataset Information

Statins affect the presentation of endothelial chemokines by targeting to multivesicular bodies.

Background

Methodology/ principal findings

Conclusions/ significance

Publications

Statins affect the presentation of endothelial chemokines by targeting to multivesicular bodies.

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