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Clin Cancer Res. 2013 Apr 15;19(8):1949-59. doi: 10.1158/1078-0432.CCR-12-3027. Epub 2013 Mar 6.

C-Reactive protein downregulates TRAIL expression in human peripheral monocytes via an Egr-1-dependent pathway.

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  • 1AuDepartment of Morphology and Embryology, Laboratorio per le Tecnologie delle Terapie Avanzate Centre, University of Ferrara, Ferrara, Trieste, Italy.



To investigate the potential link between C-reactive protein (CRP), a known biomarker of acute and chronic inflammation, and TRAIL, a cytokine which plays a key role in the immune-surveillance against tumors.


Primary normal peripheral blood mononuclear cell (PBMC) and CD14(+) monocytes were exposed to recombinant CRP (1-10 μmol/L). TRAIL expression was analyzed by ELISA and/or by quantitative real-time PCR (qRT-PCR). In parallel, the potential role of the transcription factor Egr-1 was investigated by analyzing its modulation in response to CRP and by transfection experiments.


In vitro CRP exposure induced downregulation of TRAIL expression, both at the mRNA and protein level, in unfractionated PBMC and in purified CD14(+) monocytes. TRAIL downregulation was not due to a specific toxicity or to contaminating lipopolysaccharide (LPS), as shown by the lack of induction of monocyte apoptosis and by the inability of the inhibitor of LPS polymyxin B to interfere with CRP activity. Of note, CRP downregulated TRAIL expression/release in CD14(+) monocytes also in response to IFN-α, the most potent inducer of TRAIL. At the molecular level, the downmodulation of TRAIL by CRP was accompanied by a significant increase of Egr-1. Consistently, Egr-1 overexpression reduced the baseline levels of TRAIL mRNA, whereas knocking down Egr-1 counteracted the ability of CRP to downregulate TRAIL.


Our findings suggest that a chronic elevation of CRP, which occurs during systemic inflammation and often in patients with cancer, might contribute to promote cancer development and/or progression by downregulating TRAIL in immune cells.

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