This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 27/1/226    most recent 01.ATV.0000250615.27795.85v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cappello, C. Articles by Brand, K. Search for Related Content PubMed PubMed Citation Articles by Cappello, C. Articles by Brand, K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB OZONE Related Collections Cell signalling/signal transduction Lipid and lipoprotein metabolism

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:226.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Ozonized Low Density Lipoprotein (ozLDL) Inhibits NF-B and IRAK-1–Associated Signaling

Christian Cappello; Bernd Saugel; Karin C. Huth; Andreas Zwergal; Martina Krautkrämer; Christophe Furman; Mustapha Rouis; Bianca Wieser; Heike W. Schneider; Dieter Neumeier; Korbinian Brand

From the Institute of Clinical Chemistry and Pathobiochemistry (C.C., B.S., A.Z., M.K., B.W., H.W.S., D.N., K.B.), Klinikum rechts der Isar, Technische Universität München, Germany; the Department of Restorative Dentistry and Periodontology (K.C.H.), Ludwig-Maximilians-Universität München, Germany; and INSERM U-545 and Institut Pasteur de Lille (C.F., M.R.), Lille, France.

Correspondence to Korbinian Brand, MD, PhD, Institute of Clinical Chemistry and Pathobiochemistry, Technische Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675 München, Germany. E-mail brand{at}klinchem.med.tum.de

Objective— 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-B system, as a paradigm for inflammatory signaling.

Methods and Results— We showed that activation of NF-B 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 IB proteolysis and a reduction of B-dependent transcription/target-gene expression. Furthermore, ozLDL markedly lowered stimulus-induced IB 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.

Conclusion— Our study demonstrated that ozLDL inhibited NF-B and IRAK-1–associated signaling which may impair immune function and promote apoptosis.

Evidence suggests that ozone plays a role in atherosclerosis. We demonstrated that ozone-modified LDL (ozLDL) selectively and reversibly inhibited the NF-B system, with an accompanying reduction in IRAK-1 phosphorylation/proteolysis. Cholesterol ozonization products were identified as active components. Such inhibition may impair immune function and induce apoptosis.

Key Words: ozone • ozonized LDL • atherosclerosis • NF-B • IRAK-1

This article has been cited by other articles:

				J. W. Hollingsworth, S. R. Kleeberger, and W. M. Foster Ozone and Pulmonary Innate Immunity Proceedings of the ATS, July 1, 2007; 4(3): 240 - 246. [Abstract] [Full Text] [PDF]