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      Sublytic Complement Injury Does Not Activate NF-κB, or Induce Mitogenesis in Rat Mesangial Cells

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          Sublytic complement injury to glomerular mesangial cells, mediated by the terminal membrane attack complex of complement (C5b-9), is a potential initiating mechanism in IgA nephropathy. Sublytic complement injury has been reported to result in the production of a variety of pro-inflammatory molecules and growth factors, including many regulated by the transcription factor NF-κB. To determine the importance of complement injury in the pro-inflammatory signalling which occurs in IgA nephropathy, we investigated NF-κB activation following sublytic complement injury to cultured rat glomerular mesangial cells (RMCs). A sublytic dose of rabbit anti-Thy 1.1 (THY) serum and normal human serum was selected based upon flow cytometry, chromium-release assay, and induction of superoxide production. No significant C5b-9-induced NF-κB activation was detected by electrophoretic mobility shift assays, luciferase activity of RMCs transfected with a NF-κB-driven luciferase reporter construct, nor by Northern blots for the NF-κB-responsive mRNA species monocyte chemoattractant protein-1 or IκBα. Furthermore, measurements of <sup>3</sup>H incorporation following sublytic complement injury showed inhibition of mesangial cell mitogenesis in comparison to the heat-inactivated serum treatment and to THY alone. The results of this study suggest that sublytic complement injury to RMC does not directly activate NF-κB nor induce mesangial cell proliferation in mesangial cells. Other mechanisms such as IgA immune complex formation must be required to produce these events in IgA nephropathy.

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          Author and article information

          Nephron Exp Nephrol
          Cardiorenal Medicine
          S. Karger AG
          October 2000
          31 July 2000
          : 8
          : 4-5
          : 291-298
          Immunology Research Centre, St. Vincent’s Hospital, Melbourne, Australia
          20681 Exp Nephrol 2000;8:291–298
          © 2000 S. Karger AG, Basel

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          Page count
          Figures: 5, References: 26, Pages: 8
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          Original Paper

          Cardiovascular Medicine, Nephrology

          Mitogenesis, Mesangial cell, NF-ĸB, Complement, Sublytic


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