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.
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.
Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
Yu
Y
Wei
Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
Xiaoxun
X
Sun
Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
Minhui
M
Hua
Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
Wenfeng
W
Tan
Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
Fang
F
Wang
Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
Miaojia
M
Zhang
D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D001578:Benzopyrans / Q000008:administration & dosage*; D002478:Cells, Cultured; D002867:Chromones / Q000008:administration & dosage*; D016207:Cytokines / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000276:immunology; D053245:RANK Ligand / Q000276:immunology; D013449:Sulfonamides / Q000008:administration & dosage*; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D001578:Benzopyrans; D002867:Chromones; D016207:Cytokines; C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D053245:RANK Ligand; D013449:Sulfonamides; C505688:TNFSF11 protein, human; C077313:T 614; C519076:iguratimod; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3