C-reactive protein induces G2/M phase cell cycle arrest and apoptosis in monocytes through the upregulation of B-cell translocation gene 2 expression

• C-reactive protein upregulates the expression of B-cell translocation gene 2 (BTG2).
• CRP-induced BTG2 upregulation happens via the CRP-CD32-Nox2-p53-BTG2 pathway.
• Enhanced BTG2 induces G2/M cell cycle arrest and apoptotic changes in monocytes ex vivo.
• BTG2 co-localizes with CRP and p53 in the atheromatous plaque enriched with monocytes/macrophages.

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.