Oxysterols induce interleukin‐1β production in human macrophages

Rosklint, T.; Ohlsson, Björn; Wiklund, Olov; Norén, K.; Hultén, Lillemor Mattsson

doi:10.1046/j.1365-2362.2002.00931.x

Cited by 71 publications

(48 citation statements)

References 41 publications

(59 reference statements)

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“…Under in vivo conditions, the oxysterols are always present together with a very high excess of cholesterol, and this cholesterol may decrease or prevent the activity of the oxysterol ( 31 ). It has been reported that 25-hydroxycholesterol induces production of interleukin 1 ␤ and interleukin 8 from human macrophages ( 32,33 ). It cannot be excluded that a local interleukin release as a consequence of the high levels of 25-hydroxycholesterol may be of pathogenetic importance in the SPG5 patients.…”

Section: Discussionmentioning

confidence: 99%

Marked accumulation of 27-hydroxycholesterol in SPG5 patients with hereditary spastic paresis

Schüle

Siddique

Deng

et al. 2010

Journal of Lipid Research

102

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Section: Discussionmentioning

confidence: 99%

Marked accumulation of 27-hydroxycholesterol in SPG5 patients with hereditary spastic paresis

Schüle

Siddique

Deng

et al. 2010

Journal of Lipid Research

102

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“…Cellular accumulation of 7-ketocholesterol leads to increased production of reactive oxygen species and induces apoptosis in various cell types, including macrophages, endothelial cells, and smooth muscle cells (12)(13)(14)(15). In addition, oxysterols induce inflammatory gene expression in monocytemacrophages (34)(35)(36)(37). Therefore, 7-ketocholesterol and related oxysterols probably have an important role in the pathogenesis of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1

Terasaka

Wang

Yvan‐Charvet

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

248

177

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Oxidized sterols consumed in the diet or formed on low-density lipoprotein (LDL) are toxic to endothelial cells and macrophages and are thought to have a central role in promoting atherogenesis. The ATP-binding cassette transporter ABCG1 was recently shown to promote efflux of cholesterol from macrophages to high-denisty lipoprotein (HDL). We show that HDL protects macrophages from apoptosis induced by loading with free cholesterol or oxidized LDL.The protective effect of HDL was reduced in Abcg1 ؊/؊ macrophages, especially after loading with oxidized LDL. Similarly, HDL exerted a protective effect against apoptosis induced by 7-ketocholesterol, the major oxysterol present in oxidized LDL and atherosclerotic lesions, in Abcg1 ؉/؉ , but not in Abcg1 ؊/؊ macrophages. In transfected 293 cells, efflux of 7-ketocholesterol and related oxysterols was completely dependent on expression of ABCG1 and the presence of HDL in media. In contrast, ABCA1 and apoA-1 did not stimulate the efflux of 7-ketocholesterol into media. HDL stimulated the efflux of 7-ketocholesterol from Abcg1 ؉/؉ , but not from Abcg1 ؊/؊ macrophages. In Abcg1 ؊/؊ mice fed a high-cholesterol diet, plasma levels of 7-ketocholesterol were reduced, whereas their macrophages accumulated 7-ketocholesterol. These findings indicate a specific role for ABCG1 in promoting efflux of 7-ketocholesterol and related oxysterols from macrophages onto HDL and in protecting these cells from oxysterolinduced cytotoxicity.atherosclerosis ͉ ATP-binding cassette transporter ͉ cholesterol efflux ͉ oxysterol

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“…Paul et al showed that CRP is present in the human arterial intima of atherosclerotic lesions by histological examination 45) ; furthermore, Kobayashi et al reported that, using a sample from directional coronary atherectomy, the expression of CRP was colocalized with p22phox, and CRP directly induced p22phox expression, generating reactive oxygen species in cultured smooth muscle cells 46) . Therefore, CRP may promote the production of 7-KCHO in coronary artery plaques, consequently increasing s-7KCHO, however, some reports have indicated that oxysterol influences proinflammatory properties [47][48][49][50][51] . Joffre et al reported that 7KCHO enhanced interleukin-8 gene expression using porcine retinal pigment epithelial cells 51) .…”

Section: Relation Between Concentration Of S-7kcho and Inflammationmentioning

confidence: 99%

Clinical Significance of Serum 7-Ketocholesterol Concentrations in the Progression of Coronary Atherosclerosis

Hatori

Takahashi

Iizuka

et al. 2009

J Atheroscler Thromb

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Aim: 7-Ketocholesterol concentrations can be measured in a blood sample; however, the relationship between blood 7-ketocholesterol concentrations and atherosclerotic disease is not well-known. The aim of this study was to clarify the clinical significance of serum 7-ketocholesterol concentrations (s-7KCHO) in the progression of coronary atherosclerosis. Methods: One hundred and thirty-nine subjects with coronary artery disease (CAD, subjects with stable angina pectoris or acute myocardial infarction) and 43 subjects with normal coronary arteries were enrolled in the study. s-7KCHO was measured using gas chromatography mass spectrometry. Results: s-7KCHO was significantly higher in subjects with CAD than in those with normal coronary arteries (normal coronary artery: 19.0 11.3 ng/mL, CAD: 32.4 23.1 ng/mL, p 0.01). Furthermore, patients with multiple vessel disease had significantly higher s-7KCHO than those with single vessel disease. Multivariate analysis revealed that s-7KCHO was an independent variable for CAD (p 0.01). In CAD subjects, the presence of acute myocardial infarction, number of affected vessels, and high sensitive C-reactive protein concentrations strongly correlated with s-7KCHO (p 0.01, 0.05, 0.05, respectively). Conclusion: These results indicate that high s-7KCHO is closely associated with the progression of coronary atherosclerosis and inflammation.

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Oxysterols induce interleukin‐1β production in human macrophages

Abstract: Our results show that oxysterols, and 25-hydroxycholesterol in particular, may modulate the inflammatory response in human macrophages. Consequently the presence of oxysterols in atherosclerotic tissue may dramatically influence the effect of inflammation.

Cited by 71 publications

References 41 publications

Marked accumulation of 27-hydroxycholesterol in SPG5 patients with hereditary spastic paresis

Marked accumulation of 27-hydroxycholesterol in SPG5 patients with hereditary spastic paresis

High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1

Clinical Significance of Serum 7-Ketocholesterol Concentrations in the Progression of Coronary Atherosclerosis

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