The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Grape seed proanthocyanidin extract ameliorates murine autoimmune arthritis through regulation of TLR4/MyD88/NF-κB signaling pathway

  • Kim, Sang-Hyon (Division of Rheumatology, Department of Internal Medicine, Keimyung University Dongsan Medical Center) ;
  • Bang, Jihye (Keimyung University School of Medicine) ;
  • Son, Chang-Nam (Division of Rheumatology, Department of Internal Medicine, Keimyung University Dongsan Medical Center) ;
  • Baek, Won-Ki (Department of Microbiology, Keimyung University School of Medicine) ;
  • Kim, Ji-Min (Division of Rheumatology, Department of Internal Medicine, Keimyung University Dongsan Medical Center)
  • Received : 2016.03.04
  • Accepted : 2016.04.27
  • Published : 2018.05.01
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Abstract

Background/Aims: Grape seed proanthocyanidin extract (GSPE) has been reported to have a beneficial effect on regulating inf lammation. However, the anti-inflammatory mechanism of GSPE remains unclear. The aim of this study was to verify the influence of GSPE on the Toll-like receptor 4 (TLR4)-mediated signaling pathway in the regulation of murine autoimmune arthritis. Methods: Collagen-induced arthritis (CIA) was induced in dilute brown non-agouti (DBA)/1J mice. The mice were treated with GSPE (0 or 100 mg/kg) intraperitoneally. The severity of arthritis was assessed clinically, biochemically, and histologically. Immunostaining for TLR4 was performed. The expressions of TLR4 and downstream signaling molecules were analyzed by Western blot. The effect of GSPE on lipopolysaccharide (LPS)-induced TLR4 activation was also evaluated using RAW264.7 cells and fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis and from those with osteoarthritis. Results: GSPE attenuated the clinical severity of arthritis and decreased histological damage. GSPE treatment reduced the number of TLR4-stained cells in the synovium of mice with CIA. GSPE also downregulated the expression of TLR4, myeloid differentiation factor 88 (MyD88) and phosphorylated $I{\kappa}B{\alpha}$ synovial protein in CIA mice. Concurrently, GSPE inhibited the nuclear translocation of nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) subunits (p65 and p50). LPS-induced TLR4 activation was suppressed by GSPE in human FLS as well as in murine macrophages in vitro. Conclusions: Our results demonstrated that GSPE ameliorated CIA by regulating the $TLR4-MyD88-NF-{\kappa}B$ signaling pathway.

Keywords

Acknowledgement

Supported by : Keimyung University Dongsan Medical Center

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