Abstract
DC, when fully matured are the APC best able to activate naïve T cells. Recently, we demonstrated using adenoviruses overexpressing IkappaBalpha and proteosome inhibitors that NF-kappaB is involved in DC activation, but the role of the individual subunits is still not clear. We investigated the role of the NF-kappaB subunits RelB and p50 in human DC activation using adenoviral vectors expressing RelB or p50. Nuclear RelB, in the form of RelB/p50, was active only in DC infected with both viruses, this induced the production of the soluble homeostatic chemokine CCL19, but not other homeostatic chemokines, particularly in LPS-matured DC. However, RelB/p50 did not affect the expression of costimulatory and antigen-presenting molecules, and increased the allogeneic mixed lymphocyte reaction only in LPS-matured DC. This enhanced mixed lymphocyte reaction is most likely due to enhanced CCL19 production, which sustains the interaction between mature DC and naïve T cells. In conclusion, we demonstrated that RelB/p50 was active only in DC expressing both RelB and p50, and induced CCL19 production, but not DC maturation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Antigen-Presenting Cells / cytology
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Base Sequence
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Binding Sites / genetics
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Blotting, Western
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Cell Differentiation / drug effects
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Cell Differentiation / immunology
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Chemokine CCL19 / genetics
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Chemokine CCL19 / metabolism*
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Chemokine CCL22 / metabolism
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Chemokine CXCL13 / metabolism
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Dendritic Cells / cytology
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Enzyme-Linked Immunosorbent Assay
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Humans
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I-kappa B Proteins / genetics
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I-kappa B Proteins / metabolism
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Interleukin-10 / metabolism
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Interleukin-6 / metabolism
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Lipopolysaccharides / pharmacology
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Microscopy, Fluorescence
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NF-KappaB Inhibitor alpha
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NF-kappa B p50 Subunit / genetics
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NF-kappa B p50 Subunit / metabolism*
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Protein Binding
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Transcription Factor RelB / genetics
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Transcription Factor RelB / metabolism*
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Transfection
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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CCL22 protein, human
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CXCL13 protein, human
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Chemokine CCL19
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Chemokine CCL22
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Chemokine CXCL13
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I-kappa B Proteins
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Interleukin-6
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Lipopolysaccharides
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NF-kappa B p50 Subunit
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NFKBIA protein, human
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Tumor Necrosis Factor-alpha
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Interleukin-10
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NF-KappaB Inhibitor alpha
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Green Fluorescent Proteins
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Transcription Factor RelB