The central role of nuclear factor-κB in mesangial cell activation

Abstract

Background. Nuclear factor-κB (NF-κB) is a family of transcription factors that is recognized by the KB enhancer element. Numerous proinflammatory genes have binding sites for NF-κB, and the products of these genes are an integral part of cellular activation and inflammatory response systems. Because there is a close relationship between NF-κB and mediators of cell activation, it is possible that a disruption of NF-κB-activating pathways may effectively influence mesangial cell activation. Methods. We reviewed available studies related to both NF-κB and mesangial cells in order to provide evidence for the role of NF-κB in mesangial cell activation. Results. Studies reported by this laboratory and others showed that various experimental maneuvers that modulate NF-κB activation result in a parallel modulation of proinflammatory molecule production in cultured mesangial cells. Likewise, the ability of the inhibitors of NF-κB activation to downregulate the inflammatory response in animal models of renal disease has been recently demonstrated. Conclusions. These data suggest a pivotal role of NF-κB in mesangial cell activation and designate it as an obvious target for the modulation of this activation. Studies are necessary to characterize the role of NF-κB in human renal injury. © 1999 by the International Society of Nephrology.