Transcription factor NF‐ κ B in glomerulonephritis

SUMMARY: It is becoming increasingly evident that the transcription factor, nuclear factor‐kappa B (NF‐κB) is at the heart of the inflammatory response in all tissues, including the kidney. Studies in both human glomerulonephritis and experimental disease models provide either direct or circumstantial evidence for the activation of NF‐κB. Moreover, it now appears that many existing anti‐inflammatory or immunosuppressive drugs appear to exert at least part of their action through the inhibition of NF‐κB. However, the widely used inhibitors of NF‐κB (especially steroids and cyclosporin) are not completely effective in the treatment of glomerulonephritis. These observations raise two critical questions; first, whether there are cell‐specific differences in the action of NF‐κB inhibitors and, second, whether it is more important to inhibit NF‐κB in glomerular cells or in cells of the immune system. At present, there is insufficient evidence to answer these questions as most work in this area has concentrated on NF‐κB in lymphocytes. Activation of NF‐κB in the cells of the kidney, however, suggests that they may actively contribute to inflammation. Whether agents known to inhibit NF‐κB in the immune system, such as steroids and cyclosporin, also inhibit NF‐κB in glomerular cells is not well established. Drugs able to effectively inhibit NF‐κB in tissues therefore could provide a new approach to the treatment of glomerulonephritis. It is possible that suitable agents already exist among the significant number of drugs reported to inhibit NF‐κB. If not, the recent identification of kinases that activate NF‐κB will lead to the development of agents to inhibit this central, proinflammatory pathway. It will be of great interest to determine whether they offer anything over corticosteroids and cyclosporin, the more ‘traditional’ inhibitors of NF‐κB in glomerulonephritis.