Oxidized phospholipids inhibit cyclooxygenase-2 in human macrophages via nuclear factor-κB/IκB- and ERK2-dependent mechanisms

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Abstract

Objective: Oxidized low-density lipoproteins (ox-LDL) or their components suppress macrophage inflammatory response by down-regulating cytokine synthesis, nitric oxide synthase and inducible cyclooxygenase (Cox-2). This event is crucial for the pathophysiological process leading to the formation of atherosclerotic plaque. Our present study focused on the mechanisms through which oxidized phospholipids inhibit LPS-induced Cox-2 expression in human macrophages. Methods: Macrophages were incubated with a mixture of oxidized fragmented phospholipids (ox-PAPC), present in modified LDL, and then exposed to LPS. Cox-2 was evaluated in terms of protein levels, mRNA and activity. Results: Ox-PAPC dose-dependently inhibited Cox-2 protein, mRNA and activity by preventing NF-κB binding to DNA. This effect was consequent to alterations of the degradation pattern of IκBα. Moreover, ox-PAPC markedly prevented extracellular signal-regulated kinase (ERK2) activation, leading to Cox-2 expression, whereas activation of the transcription factor peroxisome proliferator-activated receptors (PPARs) was not influenced. Conclusion: ox-PAPC down-regulates LPS-induced Cox-2 expression in human macrophages by targeting both NF-κB/IκB and ERK2 pathways. An altered inflammatory response by macrophages within atheromata may contribute to the progression of atherosclerosis.

Original languageEnglish
Pages (from-to)406-415
Number of pages10
JournalCardiovascular Research
Volume55
Issue number2
DOIs
Publication statusPublished - 2002

Fingerprint

Cyclooxygenase 2
Phospholipids
Macrophages
Atherosclerotic Plaques
Messenger RNA
Peroxisome Proliferator-Activated Receptors
Extracellular Signal-Regulated MAP Kinases
Nitric Oxide Synthase Type II
Atherosclerosis
Proteins
Transcription Factors
Down-Regulation
Cytokines
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine
DNA

Keywords

  • Atherosclerosis
  • Infection/inflammation
  • Macrophages
  • Prostaglandins
  • Signal transduction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{173d56f7c81f428dad0d79470f44e9d0,
title = "Oxidized phospholipids inhibit cyclooxygenase-2 in human macrophages via nuclear factor-κB/IκB- and ERK2-dependent mechanisms",
abstract = "Objective: Oxidized low-density lipoproteins (ox-LDL) or their components suppress macrophage inflammatory response by down-regulating cytokine synthesis, nitric oxide synthase and inducible cyclooxygenase (Cox-2). This event is crucial for the pathophysiological process leading to the formation of atherosclerotic plaque. Our present study focused on the mechanisms through which oxidized phospholipids inhibit LPS-induced Cox-2 expression in human macrophages. Methods: Macrophages were incubated with a mixture of oxidized fragmented phospholipids (ox-PAPC), present in modified LDL, and then exposed to LPS. Cox-2 was evaluated in terms of protein levels, mRNA and activity. Results: Ox-PAPC dose-dependently inhibited Cox-2 protein, mRNA and activity by preventing NF-κB binding to DNA. This effect was consequent to alterations of the degradation pattern of IκBα. Moreover, ox-PAPC markedly prevented extracellular signal-regulated kinase (ERK2) activation, leading to Cox-2 expression, whereas activation of the transcription factor peroxisome proliferator-activated receptors (PPARs) was not influenced. Conclusion: ox-PAPC down-regulates LPS-induced Cox-2 expression in human macrophages by targeting both NF-κB/IκB and ERK2 pathways. An altered inflammatory response by macrophages within atheromata may contribute to the progression of atherosclerosis.",
keywords = "Atherosclerosis, Infection/inflammation, Macrophages, Prostaglandins, Signal transduction",
author = "Sonia Eligini and Marta Brambilla and Cristina Banfi and Marina Camera and Luigi Sironi and Barbieri, {Silvia Stella} and Johan Auwerx and Elena Tremoli and Susanna Colli",
year = "2002",
doi = "10.1016/S0008-6363(02)00437-6",
language = "English",
volume = "55",
pages = "406--415",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Oxidized phospholipids inhibit cyclooxygenase-2 in human macrophages via nuclear factor-κB/IκB- and ERK2-dependent mechanisms

AU - Eligini, Sonia

AU - Brambilla, Marta

AU - Banfi, Cristina

AU - Camera, Marina

AU - Sironi, Luigi

AU - Barbieri, Silvia Stella

AU - Auwerx, Johan

AU - Tremoli, Elena

AU - Colli, Susanna

PY - 2002

Y1 - 2002

N2 - Objective: Oxidized low-density lipoproteins (ox-LDL) or their components suppress macrophage inflammatory response by down-regulating cytokine synthesis, nitric oxide synthase and inducible cyclooxygenase (Cox-2). This event is crucial for the pathophysiological process leading to the formation of atherosclerotic plaque. Our present study focused on the mechanisms through which oxidized phospholipids inhibit LPS-induced Cox-2 expression in human macrophages. Methods: Macrophages were incubated with a mixture of oxidized fragmented phospholipids (ox-PAPC), present in modified LDL, and then exposed to LPS. Cox-2 was evaluated in terms of protein levels, mRNA and activity. Results: Ox-PAPC dose-dependently inhibited Cox-2 protein, mRNA and activity by preventing NF-κB binding to DNA. This effect was consequent to alterations of the degradation pattern of IκBα. Moreover, ox-PAPC markedly prevented extracellular signal-regulated kinase (ERK2) activation, leading to Cox-2 expression, whereas activation of the transcription factor peroxisome proliferator-activated receptors (PPARs) was not influenced. Conclusion: ox-PAPC down-regulates LPS-induced Cox-2 expression in human macrophages by targeting both NF-κB/IκB and ERK2 pathways. An altered inflammatory response by macrophages within atheromata may contribute to the progression of atherosclerosis.

AB - Objective: Oxidized low-density lipoproteins (ox-LDL) or their components suppress macrophage inflammatory response by down-regulating cytokine synthesis, nitric oxide synthase and inducible cyclooxygenase (Cox-2). This event is crucial for the pathophysiological process leading to the formation of atherosclerotic plaque. Our present study focused on the mechanisms through which oxidized phospholipids inhibit LPS-induced Cox-2 expression in human macrophages. Methods: Macrophages were incubated with a mixture of oxidized fragmented phospholipids (ox-PAPC), present in modified LDL, and then exposed to LPS. Cox-2 was evaluated in terms of protein levels, mRNA and activity. Results: Ox-PAPC dose-dependently inhibited Cox-2 protein, mRNA and activity by preventing NF-κB binding to DNA. This effect was consequent to alterations of the degradation pattern of IκBα. Moreover, ox-PAPC markedly prevented extracellular signal-regulated kinase (ERK2) activation, leading to Cox-2 expression, whereas activation of the transcription factor peroxisome proliferator-activated receptors (PPARs) was not influenced. Conclusion: ox-PAPC down-regulates LPS-induced Cox-2 expression in human macrophages by targeting both NF-κB/IκB and ERK2 pathways. An altered inflammatory response by macrophages within atheromata may contribute to the progression of atherosclerosis.

KW - Atherosclerosis

KW - Infection/inflammation

KW - Macrophages

KW - Prostaglandins

KW - Signal transduction

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