Interferon-γ Induces Downregulation of Tangier Disease Gene (ATP-Binding-Cassette Transporter 1) in Macrophage-Derived Foam Cells

Panousis, Constantinos G.; Zuckerman, Steven H.

doi:10.1161/01.atv.20.6.1565

Cited by 116 publications

(71 citation statements)

References 47 publications

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“…As a general rule, proinflammatory cytokines, tumor necrosis factor α (TNF), interleukin-1β (IL-1β) and interferon-γ down-regulate the LXR-mediated enhancement of ABCA1 transcription and protein expression [64,76], whereas transforming growth factor β (TGF β) has the reverse effect and induces ABCA1 expression [77]. These results reinforce the recent findings of multiple crossroads between cellular handling of cholesterol and inflammatory responses mostly mediated at the LXR level.…”

Section: Crosstalks With Immune Regulatory Pathwayssupporting

confidence: 69%

ABCA1, from pathology to membrane function

Zarubica

Trompier

Chimini

2006

Pflugers Arch - Eur J Physiol

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The ABCA1 transporter is the prototype of the A class of mammalian adenosine triphosphate binding cassette transporters and one of the largest members of this family. ABCA1 has been originally identified as an engulfment receptor on macrophages and, more recently, it has been shown to play an essential role in the handling of cellular lipids. Indeed by promoting the effluxes of membrane phospholipids and cholesterol to lipid-poor apoprotein acceptors, ABCA1 controls the formation of high-density lipoproteins and thus the whole process of reverse cholesterol transport. A number of additional phenotypes have been found in the mouse model of invalidation of the ABCA1 gene. In spite of their clinical diversity, they all are extremely sensitive to variations in the physicochemical properties of the cell membrane, which ABCA1 controls as a lipid translocator.

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Section: Crosstalks With Immune Regulatory Pathwayssupporting

confidence: 69%

ABCA1, from pathology to membrane function

Zarubica

Trompier

Chimini

2006

Pflugers Arch - Eur J Physiol

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“…signals elicited under various pathophysiologic conditions. The signals that up-regulate the expressions of ACAT1 in monocytes-derived macrophage include steroid hormones such as dexamethasone, interferon-␥, and vitamin D 3 Maung et al, 2001;Panousis and Zuckerman, 2000;Yang et al, 2001). In the future, it will be interesting to find out whether these or other agents can up-regulate the ACAT2 expression in macrophages.…”

Section: Discussionmentioning

confidence: 99%

Acyl-Coenzyme A:Cholesterol Acyltransferase 2 (ACAT2) Is Induced in Monocyte-Derived Macrophages: In Vivo and In Vitro Studies

Sakashita

Miyazaki

Chang

et al. 2003

Laboratory Investigation

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SUMMARY:To test the possibility that acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) may be expressed in human macrophages under pathologic conditions, we employed specific anti-ACAT2 antibodies and found clear ACAT2 signals in lipid-laden as well as lipid-free macrophages under various disease conditions, including atherosclerosis. However, no ACAT2 signal was detectable in macrophages under normal physiologic conditions. Using cultured human macrophages derived from blood-borne monocytes, immunoblot and RT-PCR analyses demonstrated that immature macrophages expressed only ACAT1, but the fully differentiated macrophages expressed both ACAT1 and ACAT2. Furthermore, RT-PCR clearly revealed the presence of both ACAT1 and ACAT2 mRNAs in human atherosclerotic aorta. Double immunohistochemical staining indicated that in human atherosclerotic aorta, all macrophages expressed ACAT1, while approximately 70% to 80% of macrophages also expressed ACAT2. In congenital hyperlipidemic mice, immunohistochemistry and RT-PCR demonstrated that ACAT2 was also present in lipid-laden cells of the atheromatous plaques. Our results suggest that in atherosclerotic plaque, the ability of macrophage foam cell transformation may be augmented by the dual expressions of ACAT1 and ACAT2. Additional immunoblot and RT-PCR experiments showed that the ACAT2 signal was clearly detectable in thioglycollate-elicited exudate mouse macrophages but not in peritoneal resident macrophages. We conclude that under various pathologic conditions, fully differentiated macrophages express ACAT2 in addition to ACAT1. (Lab Invest 2003, 83:1569 -1581.

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“…Decrease in HDL-cholesterol may be related to high concentrations of phospholipase A 2 (ref. 55 ), or to downregulation of the ATP-binding cassette transporter-1 gene 56 . Increased TNF production in patients with septic shock has been shown to correlate with low total cholesterol concentration and concentrations of apolipoproteins A 1 and B (ref.…”

Section: Mechanisms Of Cholesterol Defi Ciencymentioning

confidence: 99%

Hypocholesterolemia in Clinically Serious Conditions - Review

Vyroubal¹,

Chiarla²,

Giovannini³

et al. 2008

BIOMED PAP

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Background:Cholesterol is an essential component of cell membranes, precursor of steroids, biliary acids and other components of serious importance in live organism. Cholesterol synthesis is a complicated and energy-demanding process. Real daily need of cholesterol and mechanisms of decline cholesterol levels in critical ill are unknown. During stressful situations a signifi cant hypocholesterolaemia may be found. Hypocholesterolemia has been known for a number of years to be a signifi cant prognostic indicator of increased morbidity and mortality connected with a whole spectrum of pathological conditions. The aim of article is the elucidation of the role and importance of hypocholesterolaemia during the intensive care. . Methods and Results:We examined studies that are engaged in problems of hypocholesterolemia in critically ill. Very low levels of total as well as LDL cholesterol are most frequently found in serious polytrauma, after extensive surgery, in serious infections, in protracted hypovolemic shock. It is still not clear whether hypocholesterolemia refl ects only a serious metabolic disorder, which results from a life-threatening condition, or whether it has an active role in evolution and outcome.Conclusions: Hypocholesterolemia is commonly observed in critically ill patients. Nevertheless, it is not known whether it is a secondary manifestation of disease, or whether it actively contributes to deterioration of the disease. Although the contribution of hypocholesterolemia to mortality is modest compared with known risk factors such as increased severity of illness and the development of nosocomial infection, low serum lipid concentrations represent a potential therapeutic target in sepsis.

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Interferon-γ Induces Downregulation of Tangier Disease Gene (ATP-Binding-Cassette Transporter 1) in Macrophage-Derived Foam Cells

Cited by 116 publications

References 47 publications

ABCA1, from pathology to membrane function

ABCA1, from pathology to membrane function

Acyl-Coenzyme A:Cholesterol Acyltransferase 2 (ACAT2) Is Induced in Monocyte-Derived Macrophages: In Vivo and In Vitro Studies

Hypocholesterolemia in Clinically Serious Conditions - Review

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