title: Bufalin, a bioactive component of the Chinese medicine chansu, inhibits inflammation and invasion of human rheumatoid arthritis fibroblast-like synoviocytes.
abstract: Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) contribute to the destruction of cartilage and bone by production of metalloproteinases (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM). Bufalin, a major component of Venenum Bufonis, can attenuate the invasion of various cancer cells. Here, we investigated the effects of bufalin on tumor necrosis factor-alpha (TNF-α)-induced invasion of RAFLSs. Western blot analysis and electrophoretic mobility shift assay were conducted to analyze the nuclear translocation of p65/nuclear factor-kappa B (NF-κB) and NF-κB DNA-binding activity. Semiquantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were performed to assess the expression of cytokines. Our results revealed that TNF-α significantly increased p65 translocation into nucleus (P < 0.01) and enhanced NF-κB DNA-binding activity, which were dose-dependently inhibited by bufalin. Furthermore, bufalin attenuated the TNF-α-induced interleukin-1beta (IL-1β), IL-6, and IL-8 production in RAFLSs in a concentration-dependent manner. Interestingly, TNF-α-induced invasion of RAFLSs was dampened by the pretreatment of bufalin. Additionally, bufalin decreased the mRNA abundance and secretion of MMP-9 in TNF-α-treated RAFLSs. Our results reveal that bufalin can inhibit TNF-α-induced NF-κB activation, cytokine production, invasion, and MMP-9 expression in RAFLSs, indicating a therapeutic potential of bufalin on RA.
authors: Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China, xiaofengrong2000@163.com.
authors: Xiaofeng
authors: X
authors: Rong
authors: Weidong
authors: W
authors: Ni
authors: Yongguang
authors: Y
authors: Liu
authors: Jun
authors: J
authors: Wen
authors: Chunyan
authors: C
authors: Qian
authors: Linke
authors: L
authors: Sun
authors: Jiajia
authors: J
authors: Wang
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D002018:Bufanolides / Q000494:pharmacology*; D002356:Cartilage / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D016328:NF-kappa B / Q000378:metabolism; D013582:Synovial Fluid / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002018:Bufanolides; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C095591:chan su; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C022777:bufalin