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Ozonized low density lipoprotein (ozLDL) inhibits NF-kappaB and IRAK-1-associated signaling

Ozonized low density lipoprotein (ozLDL) inhibits NF-kappaB and IRAK-1-associated signaling

Arteriosclerosis, Thrombosis, and Vascular Biology 27(1): 226-232

Recent studies have provided strong evidence for the presence of ozone in atherosclerotic lesions. In addition, modification of LDL has been suggested to be involved in atherosclerosis. In the present study we wanted to investigate whether LDL exposed to ozone (ozLDL) is able to modulate the NF-kappaB system, as a paradigm for inflammatory signaling. We showed that activation of NF-kappaB by lipopolysaccharide (LPS), a prototypic inducer of innate immunity, was reversibly inhibited by ozLDL in monocytic THP-1 cells in a dose-dependent manner, whereas tumor necrosis factor (TNF) signaling was not affected. This was not attributable to a direct ozone effect or solely the presence of lipoprotein, and neither required direct contact to LPS nor was accompanied by a change in LPS binding. Comparable inhibitory effects of ozLDL were observed in human monocyte/macrophages and endothelial cells. The presence of ozLDL led to a decrease in LPS-induced IkappaB alpha proteolysis and a reduction of kappaB-dependent transcription/target-gene expression. Furthermore, ozLDL markedly lowered stimulus-induced IkappaB kinase (IKK) activity and phosphorylation/proteolysis of interleukin (IL)-1 receptor-associated kinase-1 (IRAK-1). Finally, cholesterol ozonization products were identified as effective ozLDL inhibitory compounds. Our study demonstrated that ozLDL inhibited NF-kappaB and IRAK-1-associated signaling which may impair immune function and promote apoptosis.

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Accession: 049839720

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PMID: 17053167

DOI: 10.1161/01.ATV.0000250615.27795.85

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