title: NF-κB p65 and c-Rel subunits promote phagocytosis and cytokine secretion by splenic macrophages in cirrhotic patients with hypersplenism.
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.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. rensong1982@gmail.com
authors.forename: Song
authors.initials: S
authors.lastname: Ren
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: Manxiang
authors.initials: M
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.forename: Rongrui
authors.initials: R
authors.lastname: Liang
authors.forename: An
authors.initials: A
authors.lastname: Jiang
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Guo
authors.forename: Yansong
authors.initials: Y
authors.lastname: Pu
authors.forename: Na
authors.initials: N
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Li
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006509:Hepatitis B / Q000276:immunology / Q000378:metabolism; D006526:Hepatitis C / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006971:Hypersplenism / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D008103:Liver Cirrhosis / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis; D010655:Phenylenediamines / Q000494:pharmacology; D020569:Proto-Oncogene Proteins c-rel / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000502:physiology*; D055815:Young Adult
chemical_list: C549066:4-methyl-N1-(3-phenylpropyl)benzene-1,2-diamine; D016207:Cytokines; D010655:Phenylenediamines; D020569:Proto-Oncogene Proteins c-rel; C498143:RELA protein, human; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA