Oxidized low density lipoprotein suppresses expression of inducible cyclooxygenase in human macrophages

Sonia Eligini, Susanna Colli, Federica Basso, Luigi Sironi, Elena Tremoli

Research output: Contribution to journalArticle

Abstract

Atherogenesis involves several aspects of chronic inflammation and wound healing. Indeed, the atheroma is considered a special case of tissue response to injury. Injurious stimuli may include lipoproteins trapped within lesions where protein and lipid moieties have undergone chemical modifications. We have studied the effect of oxidized low density lipoproteins (ox-LDL) on inducible cyclooxygenase (Cox-2) in human monocyte-derived macrophages exposed to bacterial lipopolysaccharide (LPS). Levels of both Cox-2 and constitutive cyclooxygenase (Cox-1) were assessed using Western blot analysis. Prior incubation of macrophages with ox-LDL resulted in a strong inhibition of Cox-2 induced by LPS, without effect on Cox-1. The inhibitory effect was dependent on ox-LDL concentration and its onset was early in time (already detectable 1 hour after macrophage exposure to ox-LDL). Native LDL, and other forms of modified LDL, were without effect. The inhibition was dependent on endocytosis of ox-LDL and could be reproduced using the lipid extract from ox-LDL. Lysophosphatidylcholine, 7β-hydroxycholesterol, and 7- oxocholesterol failed to mimic the inhibition, but oxidized arachidonic acid- containing phospholipids, produced by autoxidation of 1-palmitoyl-2- arachidonoyl-sn-glycero-3-phosphocholine, markedly inhibited Cox-2. The observation that ox-LDL downregulates Cox-2 in human macrophages may explain the fact that, within atheromata, the transformation of macrophages into foam cells results in attenuation of the inflammatory response, thus contributing to progression of atherogenesis.

Original languageEnglish
Pages (from-to)1719-1725
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume19
Issue number7
Publication statusPublished - 1999

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Prostaglandin-Endoperoxide Synthases
Macrophages
Atherosclerotic Plaques
Lipopolysaccharides
Atherosclerosis
Hydroxycholesterols
Lipids
oxidized low density lipoprotein
Cyclooxygenase 1
Foam Cells
Lysophosphatidylcholines
Cyclooxygenase 2
Endocytosis
Arachidonic Acid
Wound Healing
Lipoproteins
Phospholipids
Down-Regulation
Western Blotting
Inflammation

Keywords

  • Atherosclerosis
  • Cyclooxygenase-2
  • Macrophages
  • Oxidized lipoproteins
  • Oxidized phospholipids

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Oxidized low density lipoprotein suppresses expression of inducible cyclooxygenase in human macrophages",
abstract = "Atherogenesis involves several aspects of chronic inflammation and wound healing. Indeed, the atheroma is considered a special case of tissue response to injury. Injurious stimuli may include lipoproteins trapped within lesions where protein and lipid moieties have undergone chemical modifications. We have studied the effect of oxidized low density lipoproteins (ox-LDL) on inducible cyclooxygenase (Cox-2) in human monocyte-derived macrophages exposed to bacterial lipopolysaccharide (LPS). Levels of both Cox-2 and constitutive cyclooxygenase (Cox-1) were assessed using Western blot analysis. Prior incubation of macrophages with ox-LDL resulted in a strong inhibition of Cox-2 induced by LPS, without effect on Cox-1. The inhibitory effect was dependent on ox-LDL concentration and its onset was early in time (already detectable 1 hour after macrophage exposure to ox-LDL). Native LDL, and other forms of modified LDL, were without effect. The inhibition was dependent on endocytosis of ox-LDL and could be reproduced using the lipid extract from ox-LDL. Lysophosphatidylcholine, 7β-hydroxycholesterol, and 7- oxocholesterol failed to mimic the inhibition, but oxidized arachidonic acid- containing phospholipids, produced by autoxidation of 1-palmitoyl-2- arachidonoyl-sn-glycero-3-phosphocholine, markedly inhibited Cox-2. The observation that ox-LDL downregulates Cox-2 in human macrophages may explain the fact that, within atheromata, the transformation of macrophages into foam cells results in attenuation of the inflammatory response, thus contributing to progression of atherogenesis.",
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author = "Sonia Eligini and Susanna Colli and Federica Basso and Luigi Sironi and Elena Tremoli",
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T1 - Oxidized low density lipoprotein suppresses expression of inducible cyclooxygenase in human macrophages

AU - Eligini, Sonia

AU - Colli, Susanna

AU - Basso, Federica

AU - Sironi, Luigi

AU - Tremoli, Elena

PY - 1999

Y1 - 1999

N2 - Atherogenesis involves several aspects of chronic inflammation and wound healing. Indeed, the atheroma is considered a special case of tissue response to injury. Injurious stimuli may include lipoproteins trapped within lesions where protein and lipid moieties have undergone chemical modifications. We have studied the effect of oxidized low density lipoproteins (ox-LDL) on inducible cyclooxygenase (Cox-2) in human monocyte-derived macrophages exposed to bacterial lipopolysaccharide (LPS). Levels of both Cox-2 and constitutive cyclooxygenase (Cox-1) were assessed using Western blot analysis. Prior incubation of macrophages with ox-LDL resulted in a strong inhibition of Cox-2 induced by LPS, without effect on Cox-1. The inhibitory effect was dependent on ox-LDL concentration and its onset was early in time (already detectable 1 hour after macrophage exposure to ox-LDL). Native LDL, and other forms of modified LDL, were without effect. The inhibition was dependent on endocytosis of ox-LDL and could be reproduced using the lipid extract from ox-LDL. Lysophosphatidylcholine, 7β-hydroxycholesterol, and 7- oxocholesterol failed to mimic the inhibition, but oxidized arachidonic acid- containing phospholipids, produced by autoxidation of 1-palmitoyl-2- arachidonoyl-sn-glycero-3-phosphocholine, markedly inhibited Cox-2. The observation that ox-LDL downregulates Cox-2 in human macrophages may explain the fact that, within atheromata, the transformation of macrophages into foam cells results in attenuation of the inflammatory response, thus contributing to progression of atherogenesis.

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