Interleukin-10 enhances the oxidized LDL-induced foam cell formation of macrophages by antiapoptotic mechanisms

• Published in: Journal of lipid research 2005-02, Vol.46 (2), p.211-219
• Main Authors: Halvorsen, Bente, Wæhre, Torgun, Scholz, Hanne, Clausen, Ole Petter, von der Thüsen, Jan H., Müller, Fredrik, Heimli, Hilde, Tonstad, Serena, Hall, Christian, Frøland, Stig S., Biessen, Erik A., Damås, Jan Kristian, Aukrust, Pål
• Format: Article
• Language: English
• Subjects: acute coronary syndromes; Apoptosis; Arteriosclerosis; atherosclerosis; Azo Compounds - pharmacology; Case-Control Studies; Cells, Cultured; Dose-Response Relationship, Drug; foam cell macrophages; Foam Cells - metabolism; Humans; Interleukin-10 - metabolism; Interleukin-10 - physiology; Leukocytes, Mononuclear - metabolism; Lipid Metabolism; Lipoproteins, LDL - metabolism; Macrophages - metabolism; Minor Histocompatibility Antigens; Mitochondria - metabolism; Monocytes - metabolism; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Proteins - biosynthesis; Oxygen - metabolism; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; RNA, Messenger - metabolism; RNA, Small Interfering - metabolism; Time Factors; Transfection
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M400324-JLR200

Interleukin (IL)-10 may have a therapeutic potential in atherosclerosis, but its mechanisms of action have not been clarified. Foam cell formation is a key event in atherogenesis, and apoptosis of these lipid-laden cells may promote plaque destabilization. We sought to explore whether IL-10 could have plaque-stabilizing properties in acute coronary syndromes (ACS). We studied the effect of IL-10 on oxidized low density lipoprotein (oxLDL)-stimulated THP-1 cells and monocyte-derived macrophages from ACS patients and healthy controls using different experimental approaches. Our main findings were: i) IL-10 enhances lipid accumulation in oxLDL-stimulated THP-1 macrophages, at least partly by counteracting oxLDL-induced apoptosis; ii) This antiapoptotic effect of IL-10 involves increased expression of the antiapoptotic genes Bfl-1 and Mcl-1, accompanied by protective effects on mitochondria function; iii) By silencing Bfl-1 and Mcl-1 genes using siRNAs, we were able to abolish this IL-10-mediated effect on lipid accumulation; iv) IL-10 also induced lipid accumulation in oxLDL-stimulated macrophages from patients with ACS, but not in macrophages from healthy controls; v) In ACS patients, this enhancing effect of IL-10 on lipid accumulation was accompanied by enhanced Mcl-1 expression. No such antiapoptotic effect was seen in macrophages from healthy controls. These findings suggest a new mechanism for the effect of IL-10 in atherosclerosis, possibly contributing to plaque stabilization.