Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol

Zhu, Xuewei; Owen, John S.; Wilson, Martha D.; Li, Haitao; Griffiths, Gary L.; Thomas, Michael J.; Hiltbold, Elizabeth M.; Fessler, Michael B.; Parks, John S.

doi:10.1194/jlr.m006486

Cited by 292 publications

(265 citation statements)

References 51 publications

(80 reference statements)

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“…The nuclear receptor LxR controls cholesterol metabolism in cells and tissues by regulating a range of proteins associated with the production and degradation of cholesterol [24], including the cholesterol-exporting protein ABCA1 [25]. Considering the cholesterol- degrading effects of Se supplementation, its influence on LxRα expression was also tested.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Selenium supplementation inhibits lipopolysaccharide-induced endometritis by decreasing the cholesterol content of lipid rafts

Zhao¹,

Zhu²,

Guo³

et al. 2018

Oncotarget

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We investigated the protective effects of selenium (Se) against lipopolysaccharide (LPS)-induced endometritis in mice. Female mice were fed Se-containing diets prior to being challenged with an intrauterine injection of LPS. Histopathological changes, expression of Toll-like receptor 4 (TLR4)-related signaling molecules and inflammatory cytokines, as well as tissue and lipid raft-associated cholesterol levels were measured in ex-vivo and in vitro experiments conducted with uterine tissues and cells. Results showed that Se reversed LPS-induced changes in uterine histopathology and decreased myeloperoxidase activity as well as levels of the pro-inflammatory cytokines TNF-α and IL-1β in excised uteri. Se supplementation also hampered LPS-induced TLR4 signaling by attenuating NF-κB and IRF3 expression, and promoted the degradation of cholesterol in both uterine tissues and lipid rafts from cultured endometrial cells. In these cells, Se also inhibited LPS-induced production of inflammatory cytokines, including TNF-α, IL-1β, and IL-6, and blocked expression of NF-κB and IRF3. These protective effects of Se were abolished by knocking down the cholesterol-sensing liver x receptor alpha (LxRα), which resulted in downregulation of the cholesterol efflux regulatory protein ABCA1. We conclude that the anti-inflammatory actions of Se against LPS-induced endometritis are associated with upregulation of the LxRα-ABCA1 pathway, leading to lipid raft destruction through cholesterol-depletion, which impedes the translocation of TLR4 to lipid rafts and blocks the ensuing inflammatory cascade.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Selenium supplementation inhibits lipopolysaccharide-induced endometritis by decreasing the cholesterol content of lipid rafts

Zhao¹,

Zhu²,

Guo³

et al. 2018

Oncotarget

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“…Furthermore, lipid-free apoA-I and reconstituted HDL treatment reduced the expression of chemokines and chemokine receptors in vivo and in vitro via modulation of NF-B and peroxisome proliferator-activated receptor ␥ ( 128 ). One of the potential mechanisms for the anti-infl ammatory effect of apoA-I is by mediating cellular cholesterol effl ux through ABCA1, an ATP-binding transporter ( 129,130 ). Interestingly, apoA-I has also been shown to attenuate palmitate-induced NF-B activation by reducing toll-like receptor-4 recruitment into lipid rafts ( 131 ).…”

Section: Effects Of Hdl On Endothelial Cell Apoptotic Pathwaysmentioning

confidence: 99%

High density lipoproteins and endothelial functions: mechanistic insights and alterations in cardiovascular disease

Riwanto

Landmesser

2013

Journal of Lipid Research

139

123

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“…Additional studies suggest that HDL and apoA-I are able to inhibit the capacity of antigen-presenting cells to stimulate T-cell activation. This inhibition was attributed to cholesterol efflux through ABCA1, an ATP-binding transporter (Tang et al 2009;Zhu et al 2010).…”

Section: Mechanisms Under Physiological Conditionsmentioning

confidence: 99%

Dysfunctional HDL: From Structure-Function-Relationships to Biomarkers

Riwanto

Rohrer

Eckardstein

et al. 2014

Handbook of Experimental Pharmacology

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Reduced plasma levels of HDL-C are associated with an increased risk of CAD and myocardial infarction, as shown in various prospective population studies. However, recent clinical trials on lipidmodifying drugs that increase plasma levels of HDL-C have not shown significant clinical benefit. Notably, in some recent clinical studies, there is no clear association of higher HDL-C levels with a reduced risk of cardiovascular events observed in patients with existing CAD. These observations have prompted researchers to shift from a cholesterol-centric view of HDL towards assessing the function and composition of HDL particles. Of importance, experimental and translational studies have further demonstrated various potential antiatherogenic effects of HDL. HDL has been proposed to promote macrophage reverse cholesterol transport and to protect endothelial cell functions by prevention of oxidation of LDL and its adverse endothelial effects. Furthermore, HDL from healthy subjects can directly stimulate endothelial cell production of nitric oxide and exert anti-inflammatory and antiapoptotic effects. Of note, increasing evidence suggests that the vascular effects of HDL can be highly heterogeneous and HDL may lose important anti-atherosclerotic properties and turn dysfunctional in patients with chronic inflammatory disorders. A greater understanding of mechanisms of action of HDL and its altered vascular effects is therefore critical within the context of HDL-targeted therapies.

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Macrophage ABCA1 reduces MyD88-dependent Toll-like receptor trafficking to lipid rafts by reduction of lipid raft cholesterol

Cited by 292 publications

References 51 publications

WITHDRAWN: Selenium supplementation inhibits lipopolysaccharide-induced endometritis by decreasing the cholesterol content of lipid rafts

WITHDRAWN: Selenium supplementation inhibits lipopolysaccharide-induced endometritis by decreasing the cholesterol content of lipid rafts

High density lipoproteins and endothelial functions: mechanistic insights and alterations in cardiovascular disease

Dysfunctional HDL: From Structure-Function-Relationships to Biomarkers

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