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Suppression of tumor necrosis factor receptor associated factor (TRAF)-2 attenuates the proinflammatory and proliferative effect of aggregated IgG on rat renal mesangial cells
Authors:Lang-Jing Zhu  Xiao Yang  Xiao-Yan Li  Qing-Hua Liu  Xue-Qing Tang  Shu-Feng Zhou  Qing-Yu Kong  Jonas Axelsson  Xue-Qing Yu
Affiliation:1. Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;2. Department of Rheumatology, The Second Affiliated Hospital, Sun Yat-sen University, Guangzhou 510120, China;3. Division of Chinese Medicine, School of Health Sciences, WHO Collaborating Center for Traditional Medicine, RMIT University, Melbourne, Vic., Australia;4. Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden;1. Beijing Key Laboratory of Mobile Computing and Pervasive Device, Institute of Computing Technology, Chinese Academy of Sciences, China;2. Pervasive Computing Research Center, Institute of Computing Technology, Chinese Academy of Sciences, China;3. University of Chinese Academy of Sciences, Beijing, China;1. Department of Pathology, Louisiana State University Health Sciences Center–Shreveport, Shreveport, LA 71104, USA;2. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA;3. Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center–Shreveport, Shreveport, LA 71104, USA;1. College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, Hubei Provincial Collaborative Innovation Center for New Energy Microgrid, China Three Gorges University, Yichang 443002, PR China;2. State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 35002, PR China;1. Department of Sciences and Methods for Engineering, University of Modena and Reggio Emilia, Via Giovanni Amendola 2, 42122 Reggio Emilia, Italy;2. N.N. Semenov Institute of Chemical Physics, Russian Academy of Sciences RAS, ulica Kosygina 4, 119991 Moscow, Russia;3. Department of Engineering “Enzo Ferrari”, University of Modena and Reggio Emilia, Via Pietro Vivarelli 10/1, 41125 Modena, Italy;1. Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA;2. Department of Neurology, University of Massachusetts Memorial Medical Center, 119 Belmont St, Worcester, MA 01605, USA
Abstract:Immune-complex (IC) mediated glomerulonephritis (GN) is a common cause of chronic kidney disease associated with increased levels of tumor necrosis factor (TNF)-α in renal cells. TNF-α signaling pathways involve complicated interactions between multiple proteins including TNF-receptor-associated factor (TRAF)-2. We have previously found markedly up-regulated expression of TRAF-2 in renal tissues from IC mediated lupus nephritis patients. Here we investigated the effect of TRAF-2 on inflammatory response in rat mesangial cells (MCs). The results showed that treatment with soluble aggregated IgG (AIgG) resulted in a time- and dose-dependent increase in the expression of interleukin (IL)-1β and IL-6. Significant cell proliferation was also observed after the treatment with soluble AIgG. Knockdown TRAF-2 by siRNA significantly suppressed soluble AIgG induced up-regulation of TRAF-2, IL-1β, and IL-6. Meanwhile the cell proliferation was inhibited and apoptotic cells were increased. It was concluded that TRAF-2 could induce the proinflammatory and proliferative effects of soluble AIgG on rat MCs. Thus, TRAF-2 may represent a future target for therapy of IC mediated GN.
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