Journal of Lipid Research (Feb 2005)
Interleukin-10 enhances the oxidized LDL-induced foam cell formation of macrophages by antiapoptotic mechanisms
- Bente Halvorsen,
- Torgun Wæhre,
- Hanne Scholz,
- Ole Petter Clausen,
- Jan H. von der Thüsen,
- Fredrik Müller,
- Hilde Heimli,
- Serena Tonstad,
- Christian Hall,
- Stig S. Frøland,
- Erik A. Biessen,
- Jan Kristian Damås,
- Pål Aukrust
Affiliations
- Bente Halvorsen
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Torgun Wæhre
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Hanne Scholz
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Ole Petter Clausen
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Jan H. von der Thüsen
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Fredrik Müller
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Hilde Heimli
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Serena Tonstad
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Christian Hall
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Stig S. Frøland
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Erik A. Biessen
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Jan Kristian Damås
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Pål Aukrust
- Research Institute for Internal Medicine, The National Hospital, Oslo, Norway; Department of Cardiology, The National Hospital, Oslo, Norway; Institute of Pathology, The National Hospital, Oslo, Norway; Institute of Microbiology, The National Hospital, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, The National Hospital, Oslo, Norway; Institute for Nutrition Research, Ullevål University Hospital, University of Oslo, Oslo, Norway; Preventive Cardiology, Ullevål University Hospital, University of Oslo, Oslo, Norway; Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research and the Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
- Journal volume & issue
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Vol. 46,
no. 2
pp. 211 – 219
Abstract
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.
