Oxidized phospholipids inhibit cyclooxygenase-2 in human macrophages via nuclear factor-κB/IκB- and ERK2-dependent mechanisms - Archive ouverte HAL Access content directly
Journal Articles Cardiovascular Research Year : 2002

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-kappaB binding to DNA. This effect was consequent to alterations of the degradation pattern of IkappaBalpha. 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-kappaB/IkappaB and ERK2 pathways. An altered inflammatory response by macrophages within atheromata may contribute to the progression of atherosclerosis.

Dates and versions

hal-04142301 , version 1 (26-06-2023)

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Sonia Eligini, Marta Brambilla, Cristina Banfi, Marina Camera, Luigi Sironi, et al.. Oxidized phospholipids inhibit cyclooxygenase-2 in human macrophages via nuclear factor-κB/IκB- and ERK2-dependent mechanisms. Cardiovascular Research, 2002, 55 (2), pp.406-415. ⟨10.1016/S0008-6363(02)00437-6⟩. ⟨hal-04142301⟩
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