NF-κB in Renal Inflammation

The NF-kappa B family of transcription factors regulates the induction and resolution of inflammation. Two main pathways, classical and alternative, control the nuclear translocation of NF-kappa B. Classical NF-kappa B activation is usually a rapid and transient response to a wide range of stimuli whose main effector is RelA/p50. The alternative NF-kappa B pathway is a more delayed response to a smaller range of stimuli resulting in DNA binding of RelB/p52 complexes. Additional complexity in this system involves the posttranslational modification of NF-kappa B proteins and an ever-increasing range of co-activators, co-repressors, and NF-kappa B complex proteins. Collectively, NF-kappa B regulates the expression of numerous genes that play a key role in the inflammatory response during human and experimental kidney injury. Multiple stimuli activate NE-kappa B through the classical pathway in somatic renal cells, and noncanonical pathway activation by TWEAK occurs in acute kidney injury. Under most test conditions, specific NF-kappa B inhibitors tend to reduce inflammation in experimental kidney injury but not always. Although many drugs in current use clinically influence NF-kappa B activation, there are no data regarding specific NF-kappa B inhibition in human kidney disease.