Caveolin isoforms in resident and elicited rat peritoneal macrophages

Kiss, Anna L.; Turi, Ágnes; Müllner, Nándor; Tı́már, József

doi:10.1078/s0171-9335(04)70038-2

Cited by 27 publications

(27 citation statements)

References 30 publications

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“…ABCA1 expression was also shown to be upregulated upon cholesterol loading of macrophages (7,27). Expression of caveolin-1 has been demonstrated in primary cultures of macrophages (18,25). As such, caveolin-1 may be involved in the regulation of cellular cholesterol metabolism.…”

Section: Caveolin Expression and Localization In Mefs And Macrophagesmentioning

confidence: 92%

Caveolin-1 and regulation of cellular cholesterol homeostasis

Frank¹,

Cheung²,

Pavlides³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

138

137

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Caveolae are 50- to 100-nm cell surface plasma membrane invaginations present in terminally differentiated cells. They are characterized by the presence of caveolin-1, sphingolipids, and cholesterol. Caveolin-1 is thought to play an important role in the regulation of cellular cholesterol homeostasis, a process that needs to be properly controlled to limit and prevent cholesterol accumulation and eventually atherosclerosis. We have recently generated caveolin-1-deficient [Cav-1(-/-)] mice in which caveolae organelles are completely eliminated from all cell types, except cardiac and skeletal muscle. In the present study, we examined the metabolism of cholesterol in wild-type (WT) and Cav-1(-/-) mouse embryonic fibroblasts (MEFs) and mouse peritoneal macrophages (MPMs). We observed that Cav-1(-/-) MEFs are enriched in esterified cholesterol but depleted of free cholesterol compared with their wild-type counterparts. Similarly, Cav-1(-/-) MPMs also contained less free cholesterol and were enriched in esterified cholesterol on cholesterol loading. In agreement with this finding, caveolin-1 deficiency was associated with reduced free cholesterol synthesis but increased acyl-CoA:cholesterol acyl-transferase (ACAT) activity. In wild-type MPMs, we observed that caveolin-1 was markedly upregulated on cholesterol loading. Despite these differences, cellular cholesterol efflux from MEFs and MPMs to HDL was not affected in the Cav-1-deficient cells. Neither ATP-binding cassette transporter G1 (ABCG1)- nor scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux was affected. Cellular cholesterol efflux to apolipoprotein A-I was not significantly reduced in Cav-1(-/-) MPMs compared with wild-type MPMs. However, ABCA1-mediated cholesterol efflux was clearly more sensitive to the inhibitory effects of glyburide in Cav-1(-/-) MPMs versus WT MPMs. Taken together, these findings suggest that caveolin-1 plays an important role in the regulation of intracellular cholesterol homeostasis and can modulate the activity of other proteins that are involved in the regulation of intracellular cholesterol homeostasis.

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Section: Caveolin Expression and Localization In Mefs And Macrophagesmentioning

confidence: 92%

Caveolin-1 and regulation of cellular cholesterol homeostasis

Frank¹,

Cheung²,

Pavlides³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

138

137

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“…The expression of caveolin-2 in macrophages was not investigated. Reports from studies on rat peritoneal macrophages suggest that resident macrophages express caveolin-1, and its expression is increased upon elicitation by Freund's adjuvant (49). The increase in caveolin-1 expression is associated with increased formation of morphologically distinguishable caveolar invaginations, as visualized by electron microscopy.…”

Section: Caveolin Expression and Localization In Various Macrophage Cmentioning

confidence: 99%

Caveolins and macrophage lipid metabolism

Gargalovic

Dory

2003

Journal of Lipid Research

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Macrophages play a pivotal role in the development of atherosclerosis. During the initial stages of the disease, monocytes migrate into the subendothelial space of blood vessels and differentiate into macrophages. The uptake of excessive amounts of lipoprotein-derived lipids leads to their conversion into foam cells (1). The availability of oxidized lipids in the subendothelial space and the macrophage-specific expression of scavenger receptors, which lack feedback regulation (2, 3), mediate the high degree of lipid enrichment. Under physiological conditions, the net accumulation of lipids in the subendothelial space of blood vessels is a result of a complex set of events, including the overall local redox balance and the rate of cholesterol accumulation/uptake and its removal via the reverse cholesterol transport pathway (4, 5).Caveolins and caveolin-1 specifically, have been implicated in the regulation of cellular cholesterol metabolism and lipid uptake, as well as efflux (6). The majority of the available information about caveolins comes primarily from studies on fibroblasts and endothelial cells, which are relatively rich in caveolae and express high amounts of caveolin-1 and caveolin-2. The evidence for caveolin expression in macrophages has been conflicting, at least in part due to the use of different macrophage-like cell lines in the various inquiries. Our laboratory has recently investigated caveolin expression in mouse primary macrophages as well as J774 cells in detail.The potential role of caveolins in the intracellular transport of cholesterol and its physical association with the cholesterol-rich rafts makes it tempting to speculate that these proteins play an important role in cholesterol metabolism of macrophages. Macrophage cholesterol metabolism may be, in turn, a central determinant in maintaining cholesterol homeostasis in the arterial wall. CAVEOLINS AND CAVEOLAELipid rafts are tightly-packed, liquid-ordered plasma membrane microdomains enriched in cholesterol, sphingomyelin, and glycolipids. They are characterized by their insolubility in non-ionic detergents at 4 Њ C and their light density on sucrose gradients. Their unique lipid composition may act to compartmentalize specific membrane proteins, including caveolins. Caveolae represent a subset of lipid rafts, characterized by high caveolin content and formation of 50-100 nm flask-shaped membrane invaginations (7).Caveolin-1, a member of the caveolin family, was first identified as a tyrosine-phosphorylated protein in Rous sarcoma virus-transformed chick embryo fibroblasts (8, 9). To-date, three mammalian caveolin genes have been identified (10). Of the three isoforms, caveolin-1 and -2 are expressed ubiq-

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“…Although it was originally thought that macrophages did not express caveolin-1 (14), recent evidence suggests that caveolin-1 is expressed in macrophages, dendritic cells, and lymphocytes (15,16). Immunoblot analysis showed that caveolin-1 was expressed in THP-1 macrophages (17,18), RAW264.7 cells (19), and peritoneal macrophages (PMs) (20). Caveolin-1 mRNA was also detected in RAW264.7 cells, J774 cells, and PMs by RT-PCR or ribonuclease protection assay (19,21).…”

mentioning

confidence: 98%

Caveolin-1 Confers Antiinflammatory Effects in Murine Macrophages via the MKK3/p38 MAPK Pathway

Wang

Kim

Song

et al. 2006

Am J Respir Cell Mol Biol

143

154

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Caveolin-1 has been reported to regulate apoptosis, lipid metabolism, and endocytosis in macrophages. In the present study, we demonstrate that caveolin-1 can act as a potent immunomodulatory molecule. We first observed caveolin-1 expression in murine alveolar macrophages by Western blotting and immunofluorescence microscopy. Loss-of-function experiments using small interfering RNA showed that down regulating caveolin-1 expression in murine alveolar and peritoneal macrophages increased LPS-induced proinflammatory cytokine TNF-alpha and IL-6 production but decreased anti-inflammatory cytokine IL-10 production. Gain-of-function experiments demonstrated that overexpression of caveolin-1 in RAW264.7 cells decreased LPS-induced TNF-alpha and IL-6 production and augmented IL-10 production. p38 mitogen-activated protein kinase (MAPK) phosphorylation was increased by overexpressing caveolin-1 in RAW264.7 cells, whereas c-Jun N-terminal kinase, extracellular signal-regulated kinase MAPK, and Akt phosphorylation were inhibited. The antiinflammatory modulation of LPS-induced cytokine production by caveolin-1 was significantly abrogated by the administration of p38 inhibitor SB203580 in RAW264.7 cells. Peritoneal macrophages isolated from MKK3 null mice did not demonstrate any modulation of LPS-induced cytokine production by caveolin-1. LPS-induced activation of NF-kappaB and AP-1 determined by electrophoretic mobility shift assay were significantly reduced by overexpressing caveolin-1 in RAW264.7 cells. The reductions were attenuated by the administration of p38 inhibitor SB203580. Taken together, our data suggest that caveolin-1 acts as a potent immunomodulatory effector molecule in immune cells and that the regulation of LPS-induced cytokine production by caveolin-1 involves the MKK3/p38 MAPK pathway.

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Caveolin isoforms in resident and elicited rat peritoneal macrophages

Cited by 27 publications

References 30 publications

Caveolin-1 and regulation of cellular cholesterol homeostasis

Caveolin-1 and regulation of cellular cholesterol homeostasis

Caveolins and macrophage lipid metabolism

Caveolin-1 Confers Antiinflammatory Effects in Murine Macrophages via the MKK3/p38 MAPK Pathway

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