Inhibitory Effect of a Novel Antirheumatic Drug T-614 on the IL-6-Induced RANKL/OPG, IL-17, and MMP-3 Expression in Synovial Fibroblasts from Rheumatoid Arthritis Patients.

Abstract

T-614 (also named as iguratimod), a novel antirheumatic drug, could attenuate joint inflammation and articular damage in rheumatoid arthritis (RA) patients, providing a new therapy for RA. Here, we tested the role T-614 on the IL-6-induced receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG), IL-17, and MMP-3 expression in synovial fibroblasts from rheumatoid arthritis (RASFs) patients. T-614 decreased RANKL expression and RANKL/OPG ratio in IL-6-induced RASFs. We confirmed this effect by a decrease of the mRNA and protein RANKL and mRNA RANKL/OPG in RASFs exposed in vitro to T-614 or MTX. Markedly decreased levels of IL-17, retinoid-related orphan receptor C (RORc), and MMP-3 mRNA expression were also observed in IL-6-induced RASFs in the presence of T-614 or MTX compared with those in its absence. Furthermore, T-614 blocked expression of p-ERK1/2 protein without affecting ERK1/2 expression, indicating that the way that T-614 regulated RANKL expression might be ERK1/2 pathway. Our results suggest that T-614 yields a strong improvement in arthritis via exact suppression of RANKL/OPG, IL-17, and MMP-3 expression in RASFs.

• Authors: Yu Wei, Xiaoxun Sun, Minhui Hua, Wenfeng Tan, Fang Wang, Miaojia Zhang
• Journal: BioMed research international (Biomed Res Int) Vol. 2015 Pg. 214683 ( 2015) ISSN: 2314-6141 [Electronic] United States
• PMID: 26273599 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antirheumatic Agents
• Benzopyrans
• Chromones
• Cytokines
• IL6 protein, human
• Interleukin-17
• Interleukin-6
• RANK Ligand
• Sulfonamides
• TNFSF11 protein, human
• T 614
• iguratimod
• MMP3 protein, human
• Matrix Metalloproteinase 3

Topics

• Antirheumatic Agents (administration & dosage)
• Arthritis, Rheumatoid (drug therapy, immunology, pathology)
• Benzopyrans (administration & dosage)
• Cells, Cultured
• Chromones (administration & dosage)
• Cytokines (immunology)
• Down-Regulation (drug effects, immunology)
• Female
• Fibroblasts (drug effects, immunology, pathology)
• Humans
• Interleukin-17 (immunology)
• Interleukin-6 (immunology)
• Male
• Matrix Metalloproteinase 3 (immunology)
• RANK Ligand (immunology)
• Sulfonamides (administration & dosage)
• Synovial Membrane (drug effects, immunology, pathology)
• Treatment Outcome