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Published: 2017-01-18

Toll-Like Receptor 4 Signaling in High Mobility Group Box-1 Protein 1 Mediated the Suppression of Regulatory T-Cells

Chunyan Luo, Huiting Liu, Hu Wang, Jiajun Wang

(School of Medical Science, Hubei University for Nationalities, Enshi, Hubei, China (mainland))

Med Sci Monit 2017; 23:300-308

DOI: 10.12659/MSM.902081


BACKGROUND: Treg cells play a central role in the suppression of immune response, and their suppressive capacity can be modulated by toll-like receptor (TLR) ligands. However, the detailed pathway of TLR ligand modulation is still unknown. The present study aimed to evaluate the effect of the high mobility group box-1 protein 1 (HMGB1) and lipopolysaccharide (LPS) on Treg cells through TLR4 signaling.
MATERIAL AND METHODS: Treg cells were purified from healthy human peripheral blood mononuclear cells (PBMCs) by magnetic-bead activity cell sorting (MACS), blocked by anti-TLR4 monoclonal antibody, and then incubated with different concentration of LPS or HMGB1. The level of gene expression of IL-1β, IL-10, IFN-γ, and TGF-β were detected using quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA), and the proliferation of Treg cells after treating by LPS and HMGB1 was analyzed by flow cytometry. The NF-κB expression in Treg cells was examined by Western blotting.
RESULTS: LPS treated CD4 CD25 Treg cells directly increased the expression of IL-1b and IL-10 and decreased the expression of IFN-γ and TGF-β. However, HMGB1 treatment resulted in a marked decreased expression of IL-1β, IL-10, IFN-γ, and TGF-β. The proliferation of CD4+ T cells was significantly inhibited by Treg cells in the LPS treatment group, but weaken in the HMGB1 treatment group. These data suggest that HMGB1 and LPS stimulation could downregulate the expression NF-κB p65 in cytoplasmic proteins and increase the expression in nuclear proteins, thus leading to modulation of IL-1β, IL-10, IFN-γ, and TGF-β expression; moreover, the... read more

Keywords: High Mobility Group Proteins, T-Lymphocytes, Regulatory, Toll-Like Receptors




Published: 2017-01-17

The Mechanism of Computed Tomography-Guided 125I Particle in Treating Lung Cancer


Jianzhong Cheng, Shaozeng Ma, Guanghua Yang, Lisen Wang, Wei Hou

Med Sci Monit 2017; 23:292-299

DOI: 10.12659/MSM.898526

Published: 2017-01-17

Asymptomatic Mild Hyperperfusion for the Prediction of Clinical Outcome in Postoperative Patients After S...


Manabu Nakagawa, Tatsushi Mutoh, Shunsuke Takenaka, Tomoko Mutoh, Tomoko Totsune, Yasuyuki Taki, Tatsuya Ishikawa

Med Sci Monit 2017; 23:285-291

DOI: 10.12659/MSM.899985