IL-6 restores dendritic cell maturation inhibited by tumor-derived TGF-β through interfering Smad 2/3 nuclear translocation
Journal
Cytokine
Journal Volume
62
Journal Issue
3
Pages
352-359
Date Issued
2013
Author(s)
Abstract
We previously found, in a canine transferable tumor model, that high concentration of IL-6 produced by tumor-infiltrating lymphocytes effectively restores the MHC expression of the tumor cells and T-cell activation inhibited by tumor-derived TGF-β. This tumor also significantly suppresses monocyte-derived dendritic cells (DCs) differentiation and the functions of differentiated DCs with unknown mechanisms. In this study, we have demonstrated that a strong reaction of IL-6 was present to neutralize TGF-β-down-regulated surface marker expression on DCs (MHC II, CD1a, CD40, CD80, CD83, CD86), TGF-β-hampered DC functions and DC-associated T-cell activation. Western blotting and confocal microscopy results indicated that the presence of IL-6 markedly decreased the nuclear concentration of a TGF-β signaling transducer, Smad 2/3. In addition, while Smad 7 is a potent molecule inhibiting Smad 2/3 nuclear translocation, no significant increase in Smad 7 gene expression upon addition of IL-6 in TGF-β-pretreated DCs was detected, which suggested that the blockage of Smad 2/3 nuclear translocation by IL-6 did not occur through a Smad 7-inhibitory mechanism. In conclusion, IL-6 inhibited TGF-β signaling and concomitantly antagonized the suppression activities of TGF-β on DC maturation and activity. This study enables further understandings of host/cancer interactions an also provide hints facilitating improvements of DC-based cancer immunotherapy. ? 2013 Elsevier Ltd.
Subjects
Dendritic cells (DCs); IL-6; Smad 2/3; TGF-β
SDGs
Other Subjects
B7 antigen; CD40 antigen; CD83 antigen; CD86 antigen; interleukin 6; major histocompatibility antigen class 2; Smad2 protein; Smad3 protein; Smad7 protein; t6 antigen; transforming growth factor beta; transforming growth factor beta antibody; antigen; interleukin 6; Smad protein; Smad2 protein; Smad3 protein; transforming growth factor beta; tumor marker; animal cell; animal venereal tumor; antigen expression; antigen presentation; article; cancer immunotherapy; cell activity; cell differentiation; cell function; cell maturation; cell nucleus; cell proliferation; concentration response; controlled study; dendritic cell; down regulation; drug efficacy; drug mechanism; immunostimulation; nonhuman; phenotype; priority journal; protein dephosphorylation; protein phosphorylation; T lymphocyte activation; tumor cell; animal; cytology; dendritic cell; dog; drug effects; metabolism; mixed lymphocyte culture; monocyte; neoplasm; pathology; protein transport; signal transduction; Animals; Antigens; Cell Differentiation; Cell Nucleus; Dendritic Cells; Dogs; Interleukin-6; Lymphocyte Culture Test, Mixed; Monocytes; Neoplasms; Phenotype; Protein Transport; Signal Transduction; Smad Proteins; Smad2 Protein; Smad3 Protein; Transforming Growth Factor beta; Tumor Markers, Biological
Type
journal article