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The protective effects of the GPR39 agonist TC-G 1008 against TNF-α-induced inflammation in human fibroblast-like synoviocytes (FLSs).

Authors
  • Jing, Weixia1
  • Sun, Wenyan2
  • Zhang, Nan3
  • Zhao, Chaoqun1
  • Yan, Xiaoping4
  • 1 Department of Rheumatism, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, 100029, China. , (China)
  • 2 Department of Pharmacology, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100102, China. , (China)
  • 3 Department of Rheumatism, Beijing China-Japan Friendship Hospital, Beijing, 100029, China. , (China)
  • 4 Department of Rheumatism, Beijing China-Japan Friendship Hospital, Beijing, 100029, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
European journal of pharmacology
Publication Date
Dec 15, 2019
Volume
865
Pages
172663–172663
Identifiers
DOI: 10.1016/j.ejphar.2019.172663
PMID: 31539553
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Rheumatoid arthritis (RA) is a common immune-mediated chronic inflammatory joint disease of unknown etiology. While tumor necrosis factor-α(TNF-α) blockers have proven to be a beneficial treatment option for many patients, not all respond to such treatments. In the present study, we investigate the role of the recently discovered zinc-sensing G protein-couple receptor GPR39. To our knowledge, this study is the first to investigate the role of GPR39 in the context of RA using human fibroblast-like synoviocytes (FLS). We found that agonism of GPR39 using its specific agonist TC-G 1008 significantly ameliorated important markers of RA, including oxidative stress, mitochondrial dysfunction, expression of proinflammatory cytokines including interleukin-1β (IL-1β), IL-6, and monocyte chemoattractant protein 1 (MCP-1), and secretion of key matrix metalloproteinases (MMPs) including MMP-1, MMP-3 and MMP-13. Furthermore, we demonstrate that these may be mediated via the Janus-kinase (JNK), activating protein 1 (AP-1), and nuclear factor-κB (NF-κB) cellular signaling pathways. Our findings demonstrate for the first time the potential of GPR39 to mediate synovial inflammation, pannus invasion, and enzymatic degradation of articular extracellular matrix. Copyright © 2019. Published by Elsevier B.V.

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