Oxidized LDL Increases and Interferon-γ Decreases Expression of CD36 in Human Monocyte–Derived Macrophages

Nakagawa, Tsutomu; Nozaki, Satoshi; Nishida, Makoto; Yakub, Janabi Mohamed; Tomiyama, Yoshiaki; Nakata, Atsuyuki; Matsumoto, Kengo; Funahashi, Tohru; Kameda‐Takemura, Kaoru; Kurata, Yoshiyuki; Yamashita, Shizuya; Matsuzawa, Yūji

doi:10.1161/01.atv.18.8.1350

Cited by 97 publications

(52 citation statements)

References 41 publications

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“…Reports using the human monocyte cell line THP-1 indicate that IFNγ and the transcription factor that it signals through, STAT1, are responsible for increased foam cell formation and CD36 expression [42,43]. By contrast, similar studies performed using primary human MDMs however are in agreement with our own [44][45][46]. Geng and Hansson, for example, found that IFNγ caused a reduction in acetylated LDL cellular association and cholesterol accumulation [44].…”

Section: Discussionsupporting

confidence: 86%

“…Geng and Hansson, for example, found that IFNγ caused a reduction in acetylated LDL cellular association and cholesterol accumulation [44]. Likewise, Nakagawa et al found that IFNγ caused a decrease in CD36 expression in primary human MDMs [45]. A recent publication by Oh et al using human MDMs from diabetic patients treated with IFNγ and LPS showed reduced cholesterol accumulation when compared with alternatively activated macrophages [46].…”

Section: Discussionmentioning

confidence: 99%

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Macrophage heterogeneity and cholesterol homeostasis: Classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL

Chu¹,

Tai²,

Beer³

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Macrophages are centrally involved during atherosclerosis development and are the predominant cell type that accumulates cholesterol in the plaque. Macrophages however, are heterogeneous in nature reflecting a variety of microenvironments and different phenotypes may be more prone to contribute towards atherosclerosis progression. Using primary human monocyte-derived macrophages, we sought to evaluate one aspect of atherogenic potential of different macrophage phenotypes by determining their propensity to associate with and accumulate oxidized low density lipoprotein (oxLDL). Classically-activated macrophages treated simultaneously with interferon γ (IFNγ) and tumour necrosis factor α (TNFα) associated with less oxLDL and accumulated less cholesterol compared to untreated controls. The combined treatment of IFNγ and TNFα reduced the mRNA expression of CD36 and the expression of both cell surface CD36 and macrophage scavenger receptor 1 (MSR1) protein. Under oxLDL loaded conditions, IFNγ and TNFα did not reduce macrophage protein expression of the transcription factor peroxisome proliferator-actived receptor γ (PPARγ) which is known to positively regulate CD36 expression. However, macrophages treated with IFNγ did prevent the PPARγ-specific agonist rosiglitazone from upregulating cell surface CD36 protein expression. Our results demonstrate that the observed reduction of cholesterol accumulation in macrophages treated with IFNγ and TNFα following oxLDL treatment was due at least in part to reduced cell surface CD36 and MSR1 protein expression.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Macrophage heterogeneity and cholesterol homeostasis: Classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL

Chu¹,

Tai²,

Beer³

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…Zhao et al (2002) reported that the p38 MAP kinase pathway may also affect PPAR-γ activation and induction of CD36 gene expression. The role of interferon-γ in CD36 regulation remains controversial, although in our hands, we observed no effect (Nakagawa, et al, 1998,Zuckerman, Panousis, Mizrahi, & Evans, 2000. As mentioned previously, CD36 interaction with apoptotic cells can lead to IL-10 secretion, and Rubic and Lorenz (2006) have reported that IL-10 decreases CD36 expression.…”

Section: Cd36 Regulationsupporting

confidence: 45%

CD36: Implications in cardiovascular disease

Febbraio

Silverstein

2007

The International Journal of Biochemistry & Cell Biology

215

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CD36 is a broadly expressed membrane glycoprotein that acts as a facilitator of fatty acid uptake, a signaling molecule, and a receptor for a wide range of ligands, including apoptotic cells, modified forms of low density lipoprotein, thrombospondins, fibrillar beta-amyloid, components of gram positive bacterial walls and malaria infected erythrocytes. CD36 expression on macrophages, dendritic and endothelial cells, and in tissues including muscle, heart, and fat, suggest diverse roles, and indeed, this is truly a multifunctional receptor involved in both homeostatic and pathologic conditions. Despite an impressive increase in our knowledge of CD36 functions, in depth understanding of the mechanistic aspects of this protein remains elusive. This review focuses on CD36 in cardiovascular disease-what we know, and what we have yet to learn.

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“…IL-4, a Th2 cytokine, has been shown to increase monocyte/Mu expression of CD36 [17], whereas expression of CD36 is down-regulated in response to a Th1 cytokine like IFN-c [32] and to LPS or dexamethasone [17].…”

Section: Discussionmentioning

confidence: 99%

IL‐13 induces expression of CD36 in human monocytes through PPARγ activation

et al. 2007

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The class B scavenger receptor CD36 is a component of the pattern recognition receptors on monocytes that recognizes a variety of molecules. CD36 expression in monocytes depends on exposure to soluble mediators. We demonstrate here that CD36 expression is induced in human monocytes following exposure to IL-13, a Th2 cytokine, via the peroxisome proliferator-activated receptor (PPAR)c pathway. Induction of CD36 protein was paralleled by an increase in CD36 mRNA. The PPARc pathway was demonstrated using transfection of a PPARc expression plasmid into the murine macrophage cell line RAW264.7, expressing very low levels of PPARc, and in peritoneal macrophages from PPARc-conditional null mice. We also show that CD36 induction by IL-13 via PPARc is dependent on phospholipase A2 activation and that IL-13 induces the production of endogenous 15-deoxy-D 12,14 -prostaglandin J 2 , an endogenous PPARc ligand, and its nuclear localization in human monocytes. Finally, we demonstrate that CD36 and PPARc are involved in IL-13-mediated phagocytosis of Plasmodium falciparum-parasitized erythrocytes. These results reveal a novel role for PPARc in the alternative activation of monocytes by IL-13, suggesting that endogenous PPARc ligands, produced by phospholipase A2 activation, could contribute to the biochemical and cellular functions of CD36.Leukocyte signaling * These 2 authors contributed equally to this work. IntroductionThe innate immune system protects the host in the early phase of infection. Circulating monocytes and tissue macrophages (Mu) mediate much of this innate immune response [1]. The strategy of recognition in the innate response is mediated by the coordinated action of pathogen-associated molecular patterns and pattern recognition receptors. Scavenger receptors and mannose receptor are important pattern recognition receptors in monocytes/Mu [2,3]. The modulation of the expression of these receptors may be critical in the role of these cells in antigen processing, scavenging, and host defence against pathogens. Several members of the scavenger receptor family, including Mu class A scavenger receptors and CD36, have been identified as receptors for modified lipoproteins on Mu, and their relevance to lipid uptake has been demonstrated in vitro and in vivo [4]. The scavenger receptor CD36, an 88-kDa integral membrane protein, is a class B scavenger receptor expressed on a wide variety of cells, in particular on monocytes and monocytederived Mu [5,6]. CD36 is known as a receptor for the uptake of oxidatively modified low-density lipoprotein (LDL) [7] and is also able to bind anionic phospholipid phosphatidylserine [8]. This scavenger receptor is implicated in the clearance of apoptotic cells [9]. Recently, McGilvray and colleagues [10] described a CD36-dependent nonopsonic phagocytosis of erythrocytes containing P. falciparum, by monocytes and culture-derived Mu, and a decrease in the parasiteinduced TNF secretion by monocytes/Mu. These processes were accentuated by CD36 up-regulation by peroxisome proliferator-acti...

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Oxidized LDL Increases and Interferon-γ Decreases Expression of CD36 in Human Monocyte–Derived Macrophages

Cited by 97 publications

References 41 publications

Macrophage heterogeneity and cholesterol homeostasis: Classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL

Macrophage heterogeneity and cholesterol homeostasis: Classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL

CD36: Implications in cardiovascular disease

IL‐13 induces expression of CD36 in human monocytes through PPARγ activation

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