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Int J Biochem Cell Biol. 2013 Feb;45(2):335-43. doi: 10.1016/j.biocel.2012.11.012. Epub 2012 Nov 26.

NF-κB p65 and c-Rel subunits promote phagocytosis and cytokine secretion by splenic macrophages in cirrhotic patients with hypersplenism.

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  • 1Department of General Surgery, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.


Transcription factors of the nuclear factor-kappa B (NF-κB) family play a key role in various biological processes. In this study, we explored the role of NF-κB in the dysfunction of splenic macrophages in hypersplenism due to liver cirrhosis. By using confocal microscopic analysis, Western Blot, TransAM NF-κB ELISA, and chromatin immunoprecipitation (ChIP), we observed that NF-κB p65, p52, and c-Rel were activated in macrophages in patients with hypersplenism (hypersplenic macrophages). Transfection of hypersplenic macrophages with a κB/luciferase reporter plasmid showed that NF-κB complexes were functional. Using co-immunoprecipitation studies, we demonstrated that p65/c-Rel dimers were activated in hypersplenic macrophages. NF-κB activation inhibitor JSH-23 and the small interfering RNA (siRNA)-mediated p65, and c-Rel gene silencing significantly blocked phagocytosis and secretion in hypersplenic macrophages. Using promoter analysis and RNA interference, we found that many phagocytotic and hepatic fibrogenetic regulators, including interleukin (IL)-1α, IL-1β, interferon-γ (IFN-γ), transforming growth factor-β1 (TGF-β1), and tumor necrosis factor-α (TNF-α), were regulated by NF-κB p65 and c-Rel in hypersplenic macrophages. Our findings demonstrate that NF-κB p65 and c-Rel play an important role in phagocytosis and secretion in hypersplenic macrophages. Activation of NF-κB p65 and c-Rel may be considered an important regulator of hypersplenism and liver cirrhosis.

Copyright © 2012 Elsevier Ltd. All rights reserved.

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