Triptolide inhibits the migration and invasion of rheumatoid fibroblast-like synoviocytes by blocking the activation of the JNK MAPK pathway.
Triptolide, a primary active ingredient extracted from a traditional Chinese herb, Tripterygium wilfordii Hook F, has been demonstrated to have a positive therapeutic effect on patients with rheumatoid arthritis (RA); however, its mechanism of action against RA is not well established. Therefore, in the present study, we observed the effect of triptolide on the aggressive behavior of RA fibroblast-like synoviocytes (RA FLSs), and we explored its underlying signal mechanisms. We found that triptolide treatment significantly reduced the migratory and invasive capacities of RA FLSs in vitro. We also demonstrated that the invasion of RA FLSs into the cartilage, evaluated in the severe combined immunodeficiency (SCID) mouse co-implantation model, was attenuated by treatment with triptolide in vivo. Additionally, the immunofluorescence results showed that triptolide treatment decreased the polymerization of F-actin and the activation of matrix metalloproteinase 9 (MMP-9). To gain insight into the molecular signal mechanisms, we determined the effect of triptolide on the activation of MAPK signal pathways. Our results indicate that triptolide treatment reduced the TNF-α-induced expression of phosphorylated JNK, but did not affect the expression of phosphorylated p38 and ERK. A JNK-specific inhibitor decreased the migration of RA FLSs. We also observed that triptolide administration improved clinical arthritic conditions and joint destruction in mice with collagen-induced arthritis (CIA). Thus, our findings suggest that the therapeutic effects of triptolide on RA might be, in part, due to its contribution to the aggressive behavior of RA FLSs.
Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China; Department of Rheumatology, Daping Hospital, Third Military Medical University, Chongqing, PR China.
Yanlong
Y
Yang
Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Yujin
Y
Ye
Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Qian
Q
Qiu
Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Youjun
Y
Xiao
Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Mingcheng
M
Huang
Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Maohua
M
Shi
Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Liuqin
L
Liang
Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China.
Xiuyan
X
Yang
Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China. Electronic address: xuhanshi@hotmail.com.
Hanshi
H
Xu
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D000070918:Synoviocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D014409:Tumor Necrosis Factor-alpha; C001899:triptolide
Aggressiveness; Fibroblast-like synoviocyte; Rheumatoid arthritis; Triptolide; c-Jun N-terminal kinase