Oxidized phospholipids inhibit cyclooxygenase-2 in human macrophages via nuclear factor-kappaB/IkappaB- and ERK2-dependent mechanisms
Articolo
Data di Pubblicazione:
2002
Citazione:
Oxidized phospholipids inhibit cyclooxygenase-2 in human macrophages via nuclear factor-kappaB/IkappaB- and ERK2-dependent mechanisms / S. Eligini, M. Brambilla, C. Banfi, M. Camera, L. Sironi, S. S. Barbieri, J. Auwerx, E. Tremoli, S. Colli. - In: CARDIOVASCULAR RESEARCH. - ISSN 0008-6363. - 55:2(2002 Aug 01), pp. 406-415. [10.1016/S0008-6363(02)00437-6]
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Macrophages; NF-kappa B; Cyclooxygenase 2; Prostaglandin-Endoperoxide Synthases; Dose-Response Relationship, Drug; Humans; Cyclooxygenase Inhibitors; Cell Culture Techniques; Cyclooxygenase 2 Inhibitors; Membrane Proteins; RNA, Messenger; Down-Regulation; I-kappa B Proteins; Isoenzymes; Lipopolysaccharides; Mitogen-Activated Protein Kinases; Lipoproteins, LDL
Elenco autori:
S. Eligini, M. Brambilla, C. Banfi, M. Camera, L. Sironi, S.S. Barbieri, J. Auwerx, E. Tremoli, S. Colli
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