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3'-Sialyllactose as an inhibitor of p65 phosphorylation ameliorates the progression of experimental rheumatoid arthritis.

Authors
  • Kang, Li-Jung1, 2, 3
  • Kwon, Eun-Soo4
  • Lee, Kwang Min5
  • Cho, Chanmi1, 2, 3
  • Lee, Jae-In6
  • Ryu, Young Bae6
  • Youm, Tae Hyun4, 7
  • Jeon, Jimin1, 2, 3
  • Cho, Mi Ra8
  • Jeong, Seon-Yong2, 9
  • Lee, Sang-Rae10, 11
  • Kim, Wook12
  • Yang, Siyoung1, 2, 3
  • 1 Department of Pharmacology, Ajou University School of Medicine, Suwon, Korea. , (North Korea)
  • 2 Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Korea. , (North Korea)
  • 3 CIRNO, Sungkyunkwan University, Suwon, Korea. , (North Korea)
  • 4 Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea. , (North Korea)
  • 5 Korea Food Research Institute, Wanju-gun, Korea. , (North Korea)
  • 6 Natural Product Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, Korea. , (North Korea)
  • 7 Laboratory of Physiology, College of Pharmacy, Chungnam National University, Daejeon, Korea. , (North Korea)
  • 8 Rheumatism Research Center, The Catholic University of Korea, College of Medicine, Seoul, Korea. , (North Korea)
  • 9 Department of Medical Genetics, Ajou University School of Medicine, Suwon, Korea. , (North Korea)
  • 10 National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Korea. , (North Korea)
  • 11 Department of Functional Genomics, University of Science and Technology, Daejeon, Korea. , (North Korea)
  • 12 Department of Molecular Science and Technology, Ajou University, Suwon, Korea. , (North Korea)
Type
Published Article
Journal
British Journal of Pharmacology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Dec 01, 2018
Volume
175
Issue
23
Pages
4295–4309
Identifiers
DOI: 10.1111/bph.14486
PMID: 30152858
Source
Medline
Language
English
License
Unknown

Abstract

3'-Sialyllactose (3'-SL) is a safe compound that is present in high levels in human milk. Although it has anti-inflammatory properties and supports immune homeostasis, its effect on collagen-induced arthritis (CIA) is unknown. In this study, we investigated the prophylactic and therapeutic effect of 3'-SL on the progression of rheumatoid arthritis (RA) in in vitro and in vivo models. The anti-arthritic effect of 3'-SL was analysed with fibroblast-like synoviocytes in vitro and an in vivo mouse model of CIA. RT-PCR, Western blotting and ELISA were performed to evaluate its effects in vitro. Histological analysis of ankle and knee joints of mice with CIA was performed using immunohistochemistry, as well as safranin-O and haematoxylin staining. 3'-SL markedly alleviated the severity of CIA in the mice by reducing paw swelling, clinical scores, incidence rate, serum levels of inflammatory cytokines and autoantibody production. Moreover, 3'-SL reduced synovitis and pannus formation and suppressed cartilage destruction by blocking secretion of chemokines, pro-inflammatory cytokines, matrix metalloproteinases and osteoclastogenesis via NF-κB signalling. Notably, phosphorylation of p65, which is a key protein in the NF-κB signalling pathway, was totally blocked by 3'-SL in the RA models. 3'-SL ameliorated pathogenesis of CIA by suppressing catabolic factor expression, proliferation of inflammatory immune cells and osteoclastogenesis. These effects were mediated via blockade of the NF-κB signalling pathway. Therefore, 3'-SL exerted prophylactic and therapeutic effects and could be a novel therapeutic agent for the treatment of RA. © 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

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