C-reactive protein induces G2/M phase cell cycle arrest and apoptosis in monocytes through the upregulation of B-cell translocation gene 2 expression |
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Authors: | Yuna Kim Jewon Ryu Min Sook Ryu Sunny Lim Ki Ok Han In Kyoung Lim Ki Hoon Han |
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Institution: | 1. Department of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;2. Department of Endocrinology and Metabolism, School of Medicine, Kwandong University, Seoul, Republic of Korea;3. Department of Biochemistry and Molecular Biology, BK21 Division of Cell Transformation and Restoration, Ajou University School of Medicine, Suwon 443-721, Republic of Korea |
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Abstract: | We hypothesized that C-reactive protein (CRP) may affect the cell cycle and induce apoptotic changes of monocytes. CRP (∼25 μg/ml) significantly increased expressions of B-cell translocation gene 2 (BTG2) mRNA and protein in human monocytes through pathways involving CD32/NADPH oxidase 2/p53, which eventually induced G2/M phase arrest and apoptotic cell death. Such pro-apoptotic effect of CRP was not found in thioglycollate-elicited intraperitoneal monocytes/macrophages harvested from BTG2-knockout male C57BL/6 mice (n = 5). Within atheromatous plaques obtained from CRP-transgenic male LDLR−/− C57BL/6 mice (n = 5) and human coronary arteries, BTG2 co-localized with CRP, p53 and monocytes/macrophages. Therefore the pro-apoptotic pathway of CRP-CD32-Nox2-p53-BTG2 may contribute to the retardation of the atherogenic process. |
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Keywords: | C-reactive protein Monocytes p53 B-cell translocation gene 2 Apoptosis Atherogenesis |
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