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Atomic Force Microscopy Study of the Anti-inflammatory Effects of Triptolide on Rheumatoid Arthritis Fibroblast-like Synoviocytes

Published online by Cambridge University Press:  26 July 2017

Zhanhui Su ,
Han Sun ,
Man Ao  and
Chunying Zhao
Zhanhui Su*
Affiliation:
Hebei Key Laboratory of Research and Development for Traditional Chinese Medicine, Institute of Chinese Materia Medica, Chengde Medical College, Chengde 067000, China
Han Sun
Affiliation:
Chengde Nursing Vocational College, Chengde 067000, China
Man Ao
Affiliation:
Affiliated Hospital of Chengde Medical College, Chengde 067000, China
Chunying Zhao
Affiliation:
Hebei Key Laboratory of Research and Development for Traditional Chinese Medicine, Institute of Chinese Materia Medica, Chengde Medical College, Chengde 067000, China
*
*Corresponding author. szh13603141833@sina.com
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Abstract

High-resolution atomic force microscopy (AFM) was used for the in situ evaluation of the anti-inflammatory effects of triptolide on rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) to understand the anti-RA effects of triptolide, based on the morphological and biophysical changes observed in RA-FLS. RA-FLS have been reported to play a primary role in inflammatory bone destruction during the development of RA and thus are regarded as an important target for RA treatment. Triptolide pretreatment significantly inhibited tumor necrosis factor-α-induced expression of the interleukin (IL)-1β, IL-6, and IL-8 genes in MH7A cells. Using AFM, we showed that triptolide-induced morphological damage in MH7A cells by inducing significant ultrastructure changes in the membrane, which were closely related to triptolide-induced apoptosis in MH7A cells. Using force measurements determined with AFM, triptolide was shown to increase the stiffness of MH7A cells. These findings not only revealed the strong anti-inflammatory effects of triptolide on RA-FLS, highlighting triptolide as a potential anti-RA agent, but also revealed the possible use of AFM for studying anti-inflammatory responses in RA-FLS, which we expect to be developed into a potential tool for anti-RA drug studies in RA-FLS.

Keywords

atomic force microscopymorphologystiffnesssynoviocytestriptolide
Type
Biological Science Applications
Information
Microscopy and Microanalysis , Volume 23 , Issue 5 , October 2017 , pp. 1002 - 1012
Copyright
© Microscopy Society of America 2017 

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References

Bartok, B. & Firestein, G.S. (2010). Fibroblast-like synoviocytes: Key effector cells in rheumatoid arthritis. Immunol Rev 233(1), 233–255.CrossRefGoogle ScholarPubMed
Bitler, A., Dover, R. & Shai, Y. (2012). Fractal properties of macrophage membrane studied by AFM. Micron 43(12), 1239–1245.CrossRefGoogle ScholarPubMed
Cai, X., Yang, X., Cai, J., Wu, S. & Chen, Q. (2010). Atomic force microscope-related study membrane-associated cytotoxicity in human pterygium fibroblasts induced by mitomycin C. J Phys Chem B 114(11), 3833–3839.CrossRefGoogle ScholarPubMed
Cross, S.E., Jin, Y.S., Rao, J. & Gimzewski, J.K. (2007). Nanomechanical analysis of cells from cancer patients. Nat Nanotechnol 2(12), 780–783.CrossRefGoogle ScholarPubMed
D’Agostino, D.P., Olson, J.E. & Dean, J.B. (2009). Acute hyperoxia increases lipid peroxidation and induces plasma membrane blebbing in human U87 glioblastoma cells. Neuroscience 159(3), 1011–1022.CrossRefGoogle ScholarPubMed
Dai, S., Yin, K., Yao, X. & Zhou, L. (2013). Inhibition of interleukin-13 gene expression by triptolide in activated T lymphocytes. Respirology 18(8), 1249–1255.CrossRefGoogle ScholarPubMed
Dokukin, M.E. & Sokolov, I. (2012). Quantitative mapping of the elastic modulus of soft materials with HarmoniX and PeakForce QNM AFM modes. Langmuir 28(46), 16060–16071.CrossRefGoogle ScholarPubMed
Dupres, V., Menozzi, F.D., Locht, C., Clare, B.H., Abbott, N.L., Cuenot, S., Bompard, C., Raze, D. & Dufrene, Y.F. (2005). Nanoscale mapping and functional analysis of individual adhesins on living bacteria. Nat Methods 2(7), 515–520.CrossRefGoogle ScholarPubMed
Fan, D., He, X., Bian, Y., Guo, Q., Zheng, K., Zhao, Y., Lu, C., Liu, B., Xu, X., Zhang, G. & Lu, A. (2016). Triptolide modulates TREM-1 signal pathway to inhibit the inflammatory response in rheumatoid arthritis. Int J Mol Sci 17(4), 498.CrossRefGoogle ScholarPubMed
Guo, H., Pan, C., Chang, B., Wu, X., Guo, J., Zhou, Y., Liu, H., Zhu, Z. & Chen, L. (2016). Triptolide improves diabetic nephropathy by regulating Th cell balance and macrophage infiltration in rat models of diabetic nephropathy. Exp Clin Endocrinol Diabetes 124(6), 389–398.Google ScholarPubMed
Guz, N., Dokukin, M., Kalaparthi, V. & Sokolov, I. (2014). If Cell Mechanics Can Be Described by Elastic Modulus: Study of Different Models and Probes Used in Indentation Experiments. Biophysical Journal 107(3), 564–575.CrossRefGoogle ScholarPubMed
Han, R., Rostami-Yazdi, M., Gerdes, S. & Mrowietz, U. (2012). Triptolide in the treatment of psoriasis and other immune-mediated inflammatory diseases. Br J Clin Pharmacol 74(3), 424–436.CrossRefGoogle ScholarPubMed
Jia, S., Zhang, S., Yuan, H. & Chen, N. (2015). Lunasin inhibits cell proliferation via apoptosis and reduces the production of proinflammatory cytokines in cultured rheumatoid arthritis synovial fibroblasts. Biomed Res Int 2015, 346839.Google ScholarPubMed
Kim, K.S., Cho, C.H., Park, E.K., Jung, M.H., Yoon, K.S. & Park, H.K. (2012). AFM-detected apoptotic changes in morphology and biophysical property caused by paclitaxel in ishikawa and HeLa cells. PLoS One 7(1), e30066.CrossRefGoogle ScholarPubMed
Kim, H.B., Lee, S.W., Mun, C.H., Yoon, J.Y., Pai, J., Shin, I., Park, Y.B., Lee, S.K. & Cho, J.W. (2015). O-linked N-acetylglucosamine glycosylation of p65 aggravated the inflammation in both fibroblast-like synoviocytes stimulated by tumor necrosis factor-alpha and mice with collagen induced arthritis. Arthritis Res The 17, 248.CrossRefGoogle ScholarPubMed
Kusunoki, N., Yamazaki, R., Kitasato, H., Beppu, M., Aoki, H. & Kawai, S. (2004). Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts. BMC Pharmacol 4, 2.CrossRefGoogle Scholar
Lee, J.W., Ok, M.R., Lee, S. & Lim, J.I. (2015). Detecting changes in arthritic fibroblast-like synoviocytes using atomic force microscopy. Microsc Res Techniq 78(11), 982–988.CrossRefGoogle ScholarPubMed
Lee, A., Qiao, Y., Grigoriev, G., Chen, J., Park-Min, K.H., Park, S.H., Ivashkiv, L.B. & Kalliolias, G.D. (2013). Tumor necrosis factor alpha induces sustained signaling and a prolonged and unremitting inflammatory response in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 65(4), 928–938.CrossRefGoogle Scholar
Lin, N., Sato, T. & Ito, A. (2001). Triptolide, a novel diterpenoid triepoxide from Tripterygium wilfordii Hook. f., suppresses the production and gene expression of pro-matrix metalloproteinases 1 and 3 and augments those of tissue inhibitors of metalloproteinases 1 and 2 in human synovial fibroblasts. Arthritis Rheum-Us 44(9), 2193–2200.3.0.CO;2-5>CrossRefGoogle Scholar
Lu, Y., Wang, W.J., Leng, J.H., Cheng, L.F., Feng, L. & Yao, H.P. (2008). Inhibitory effect of triptolide on interleukin-18 and its receptor in rheumatoid arthritis synovial fibroblasts. Inflammation Res 57(6), 260–265.CrossRefGoogle ScholarPubMed
Lv, Q., Zhu, X.Y., Xia, Y.F., Dai, Y. & Wei, Z.F. (2015). Tetrandrine inhibits migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes through down-regulating the expressions of Rac1, Cdc42, and RhoA GTPases and activation of the PI3K/Akt and JNK signaling pathways. Chin J Nat Med 13(11), 831–841.Google ScholarPubMed
Nikolaev, N.I., Muller, T., Williams, D.J. & Liu, Y. (2014). Changes in the stiffness of human mesenchymal stem cells with the progress of cell death as measured by atomic force microscopy. J Biomech 47(3), 625–630.CrossRefGoogle ScholarPubMed
Pelling, A.E., Veraitch, F.S., Chu, C.P.K., Mason, C. & Horton, M.A. (2009). Mechanical dynamics of single cells during early apoptosis. Cell Motil Cytoskel 66(7), 409–422.CrossRefGoogle ScholarPubMed
Peng, A.P., Wang, X.Y. & Zhuang, J.H. (2014). Triptolide inhibites Th17 cell differentiation via regulating cyclooxygenase-2/ prostaglandin E2 axis in synovial fibroblasts from rheumatoid arthritis. Zhongguo Zhong Yao Za Zhi 39(3), 536–539.Google ScholarPubMed
Pi, J., Cai, H., Jin, H., Yang, F., Jiang, J., Wu, A., Zhu, H., Liu, J., Su, X., Yang, P. & Cai, J. (2015a). Qualitative and quantitative analysis of ROS-mediated oridonin-induced oesophageal cancer KYSE-150 cell apoptosis by atomic force microscopy. PLoS One 10(10), e0140935.CrossRefGoogle ScholarPubMed
Pi, J., Cai, H., Yang, F., Jin, H., Liu, J., Yang, P. & Cai, J. (2015b). Atomic force microscopy based investigations of anti-inflammatory effects in lipopolysaccharide-stimulated macrophages. Anal Bioanal Chem 408(1), 165–176.CrossRefGoogle Scholar
Shao, X.T., Feng, L., Yao, H.P., Sun, W.J. & Zhang, L.H. (2004). Effect of triptolide on TNFalpha-induced activation of NF-kappaB and expression of COX-2 and iNOS in human rheumatoid arthritis synovial fibroblasts. Zhejiang Da Xue Xue Bao Yi Xue Ban 33(2), 160–165.Google ScholarPubMed
Sneddon, I.N. (1965). The relation between load and penetration in the axisymmetric boussinesq problem for a punch of arbitrary profile. Int J Eng Sci 3(1), 47–57.CrossRefGoogle Scholar
Xu, Z.T., Wu, G.S., Wei, X., Chen, X.P., Wang, Y.T. & Chen, L.D. (2013). Celastrol induced DNA damage, cell cycle arrest, and apoptosis in human rheumatoid fibroblast-like synovial cells. Am J Chinese Med 41(3), 615–628.CrossRefGoogle ScholarPubMed
Yan, C., Kong, D., Ge, D., Zhang, Y., Zhang, X., Su, C. & Cao, X. (2015). Mitomycin C induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via a mitochondrial-mediated pathway. Cell Physiol Biochem 35(3), 1125–1136.CrossRefGoogle Scholar
Yang, K.Y. & Chen, D.L. (2015). Shikonin inhibits inflammatory response in rheumatoid arthritis synovial fibroblasts via lncRNA-NR024118. Evid Based Complement Alternat Med 2015(2015), 631737.CrossRefGoogle ScholarPubMed
Yao, H., Zhou, J., Li, D., Wu, N., Bader, A., Hoxtermann, S., Altmeyer, P. & Brockmeyer, N.H. (2005). FK506 enhances triptolide-induced down-regulation of cyclooxygenase-2, inducible nitric oxide synthase as well as their products PGE2 and NO in TNF-alpha-stimulated synovial fibroblasts from rheumatoid arthritic patients. Eur J Med Res 10(3), 110–116.Google ScholarPubMed
Zhang, X.J., Shi, X.L., Xu, L., Yuan, J.H. & Fang, X.H. (2013). Atomic force microscopy study of the effect of HER 2 antibody on EGF mediated ErbB ligand-receptor interaction. Nanomed Nanotechnol 9(5), 627–635.CrossRefGoogle ScholarPubMed
Ziaei, S. & Halaby, R. (2016). Immunosuppressive, anti-inflammatory and anti-cancer properties of triptolide: A mini review. Avicenna J Phytomed 6(2), 149–164.Google ScholarPubMed