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ORIGINAL ARTICLE
Year : 2014  |  Volume : 139  |  Issue : 1  |  Page : 117-124

Validity of SW982 synovial cell line for studying the drugs against rheumatoid arthritis in fluvastatin-induced apoptosis signaling model


1 Institute of Biomaterials, Yonsei University, Wonju, Korea
2 Department of Environmental Medical Biology, Yonsei University Wonju College of Medicine, Wonju, Korea
3 Institute of Biomaterials, Yonsei University; Department of Microbiology, Yonsei University Wonju College of Medicine, Wonju, Korea
4 The Hospital for Rheumatic Diseases, Hanyang University Medical Center, Seoul, Korea
5 Department of Rheumatology, Yonsei University Wonju College of Medicine, Wonju, Korea

Correspondence Address:
Soo-Ki Kim
Department of Microbiology, Wonju College of Medicine Yonsei University 162 Ilsan-dong, Wonju, Gangwon province 220-701
Korea
Tae-Young Kang
Department of Rheumatology, Yonsei University Wonju College of Medicine Wonju, Gangwon province 220-701
Korea
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Source of Support: None, Conflict of Interest: None


PMID: 24604047

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Background & objectives: To study effects of drugs against rheumatoid arthritis (RA) synoviocytes or fibroblast like synoviocytes (FLS) are used. To overcome the drawbacks of using FLS, this study was conducted to show the validity of SW982 synovial cell line in RA study. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V propidium iodide (PI) staining, mitochondrial membrane potential assay, Triton X-114 Phase partitioning, and immunolot for apoptosis signaling in SW982 human synovial cell line were performed. Results: Fluvastatin induced apoptosis in a dose- and time-dependent manner in TNFα -stimulated SW982 human synovial cells. A geranylgeranylpyrophosphate (GGPP) inhibitor, but not a farnesylpyrophosphate (FPP) inhibitor, induced apoptosis, and fluvastatin-induced apoptosis was associated with the translocation of isoprenylated RhoA and Rac1 proteins from the cell membrane to the cytosol. Fluvastatin-induced downstream apoptotic signals were associated with inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Accordingly, 89 kDa apoptotic cleavage fragment of poly (ADP-ribose) polymerase (PARP) was detected. Interpretation & conclusions: Collectively, our data indicate that fluvastatin induces apoptotic cell death in TNFα-stimulated SW982 human synovial cells through the inactivation of the geranylgerenylated membrane fraction of RhoA and Rac1 proteins and the subsequent inhibition of the PI3K/Akt signaling pathway. This finding shows the validity of SW982 cell line for RA study.


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