Decoy receptor 3 down-regulates centrosomal protein 70 kDa specifically in rheumatoid synovial fibroblasts.

Abstract

OBJECTIVES:

Decoy receptor 3 (DcR3) competitively binds to Fas ligand, lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells (LIGHT) and TNF-like ligand 1A (TL1A), thereby preventing their effects. Using a microarray assay, we previously newly identified centrosomal protein 70 kDa (CEP70) as one of the genes whose expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLS) is reduced by DcR3. Here, we investigated the significance of DcR3 regulation of CEP70 for RA-FLS.

METHODS:

Synovial samples were obtained from RA patients who had never been treated with biologics and from osteoarthritis (OA) patients. CEP70 mRNA expression was quantified using RT-qPCR analysis. CEP70 protein expression was assessed using immunohistochemical and western blot analyses.

RESULTS:

CEP70 was expressed predominantly in the superficial lining layer in RA synovial tissue. CEP70 expression was dose-dependently downregulated by DcR3-Fc in RA-FLS but was not downregulated in OA-FLS. TL1A antibody prevented the DcR3-Fc inhibitory effects on CEP70 expression in RA-FLS.

CONCLUSIONS:

These results indicated that DcR3 reduces CEP70 expression in RA-FLS by binding to membrane-bound TL1A and may suppress RA-FLS proliferation. The reduction in CEP70 expression by DcR3/TL1A signaling may control the hyperplasia of RA synovium.

• Authors: Koji Fukuda, Yasushi Miura, Toshihisa Maeda, Shinya Hayashi, Ryosuke Kuroda
• Journal: Modern rheumatology (Mod Rheumatol) Vol. 28 Issue 2 Pg. 287-292 (Mar 2018) ISSN: 1439-7609 [Electronic] England
• PMID: 28696795 (Publication Type: Journal Article)

Chemical References

• Cell Cycle Proteins
• Cep70 protein, human
• Microtubule-Associated Proteins
• Receptors, Tumor Necrosis Factor, Member 6b
• TNFRSF6B protein, human

Topics

• Aged
• Arthritis, Rheumatoid (metabolism)
• Cell Cycle Proteins (genetics, metabolism)
• Cells, Cultured
• Down-Regulation
• Female
• Fibroblasts (metabolism)
• Humans
• Male
• Microtubule-Associated Proteins (genetics, metabolism)
• Middle Aged
• Receptors, Tumor Necrosis Factor, Member 6b (metabolism)
• Synovial Membrane (cytology, metabolism)