Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8324403 | The International Journal of Biochemistry & Cell Biology | 2013 | 9 Pages |
Abstract
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.
Keywords
IL-1αRIPAIFN-γIL-1βqRT-PCRNF-κBTGF-β1Small interfering RNAsiRNAchromatin immunoprecipitationinterferon-γInterleukin-1αInterleukin-1βTransforming growth factor β1Cytokine secretiontumor necrosis factor-αliver cirrhosisTNF-αNuclear factor-kappa B (NF-κB)Nuclear factor-kappa BPhagocytosisSplenic macrophageHBVHepatitis C virusHCVHypersplenismquantitative real-time polymerase chain reactionhepatitis B virusCHiP
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Authors
Song Ren, Shu Zhang, Manxiang Li, Chen Huang, Rongrui Liang, An Jiang, Yanfeng Guo, Yansong Pu, Na Huang, Jun Yang, Zongfang Li,