CXCL10 and TRAIL Are Upregulated by TXNDC5 in Rheumatoid Arthritis Fibroblast-like Synoviocytes

J Rheumatol. 2018 Mar;45(3):335-340. doi: 10.3899/jrheum.170170. Epub 2017 Dec 15.

Abstract

Objective: Thioredoxin domain containing 5 (TXNDC5) is highly expressed in synovial membranes of rheumatoid arthritis (RA). Our study aimed to investigate the pathogenic role of TXNDC5 in RA.

Methods: PCR arrays, CCK-8 assays, flow cytometry, and transwell migration assays were used to analyze cultured rheumatoid arthritis synovial fibroblasts (RASF).

Results: Increased CXCL10 and tumor necrosis factor-related apoptosis-inducing ligand levels were detected in RASF transfected with anti-TXNDC5 small interfering RNA (siRNA), and decreased expression was detected in RASF transfected with TXNDC5-expressing plasmids. Significantly attenuated RASF proliferation and migration, and increased RASF apoptosis, were observed in the siRNA-transfected RASF.

Conclusion: Downregulation of TXNDC5 could contribute to RASF antiangiogenic and proapoptotic features through the suppression of CXCL10 and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand).

Keywords: CXCL10; PATHWAY; RHEUMATOID ARTHRITIS; TRAIL; TXNDC5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Arthritis, Rheumatoid / pathology*
  • Arthroplasty, Replacement, Knee
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Chemokine CXCL10 / metabolism*
  • Down-Regulation
  • Female
  • Fibroblasts / metabolism*
  • Humans
  • Middle Aged
  • Protein Disulfide-Isomerases / metabolism*
  • Synovial Membrane / pathology*
  • Synoviocytes / metabolism*
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • Up-Regulation

Substances

  • CXCL10 protein, human
  • Chemokine CXCL10
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Protein Disulfide-Isomerases
  • TXNDC5 protein, human