Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-kappa B signaling in macrophages and protecting endothelial cells
机构：[1]Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School ofMedicine, Shanghai, People's Republic of China[2]Department of Orthopaedic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, People'sRepublic of China昆明医科大学附属第一医院[3]Complex and Intelligent Research Center, School of Mechanical and Power Engineering, East China University of Science and Technology, Shanghai,People's Republic of China[4]Wenshan Zhengbao Orthopaedic Hospital of Yunnan Province, Wenshan, People's Republic of China
Gouty arthritis is a rheumatic disease that is characterized by the deposition of monosodium urate (MSU) in synovial joints cause by the increased serum hyperuricemia. This study used a three-dimensional (3D) flowing microfluidic chip to screen the effective candidate against MSU-stimulated human umbilical vein endothelial cell (HUVEC) damage, and found kinsenoside (Kin) to be the leading active component of Anoectochilus roxburghi, one of the Chinese medicinal plant widely used in the treatment of gouty arthritis clinically. Cell viability and apoptosis of HUVECs were evaluated, indicating that direct Kin stimulation and conditioned medium (CM) from Kin-treated macrophages both negatively modulated with MSU crystals. Additionally, Kin was capable of attenuating MSU-induced activation of nuclear factor-kappa B/mitogen-activated protein kinase (NF-kappa B/MAPK) signaling, targeting I kappa B kinase-alpha (IKK alpha) and IKK beta kinases of macrophages and influencing the expressions of NF-kappa B downstream cytokines and subsequent HUVEC bioactivity. Inflammasome NLR pyrin domain-containing 3 (NALP3) and toll-like receptor 2 (TLR2) were also inhibited after Kin treatment. Also, Kin downregulated CD14-mediated MSU crystals uptake in macrophages. In vivo study with MSU-injected ankle joints further revealed the significant suppression of inflammatory infiltration and endothelia impairment coupled with alleviation of ankle swelling and nociceptive response via Kin treatments. Taken together, these data implicated that Kin was the most effective candidate from Anoectochilus roxburghi to treat gouty arthritis clinically.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81172549, 81672205]
第一作者机构：[1]Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School ofMedicine, Shanghai, People's Republic of China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School ofMedicine, Shanghai, People's Republic of China[3]Complex and Intelligent Research Center, School of Mechanical and Power Engineering, East China University of Science and Technology, Shanghai,People's Republic of China[*1]Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road 639, Huangpu District, Shanghai, China
推荐引用方式(GB/T 7714)：
Qiao Han,Wang Bing,Yin Di,et al.Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-kappa B signaling in macrophages and protecting endothelial cells[J].CELL DEATH & DISEASE.2016,7:doi:10.1038/cddis.2016.255.
APA：
Qiao Han,Wang Bing,Yin Di,Li Hua,Li Shi-he...&Tang Ting-ting.(2016).Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-kappa B signaling in macrophages and protecting endothelial cells.CELL DEATH & DISEASE,7,
MLA：
Qiao Han,et al."Kinsenoside screening with a microfluidic chip attenuates gouty arthritis through inactivating NF-kappa B signaling in macrophages and protecting endothelial cells".CELL DEATH & DISEASE 7.(2016)
生物学