NF-κB in Renal Inflammation

The NF-κB family of transcription factors regulates the induction and resolution of inflammation. Two main pathways, classical and alternative, control the nuclear translocation of NF-κB. Classical NF-κB activation is usually a rapid and transient response to a wide range of stimuli whose main effector is RelA/p50. The alternative NF-κB 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-κB proteins and an ever-increasing range of co-activators, co-repressors, and NF-κB complex proteins. Collectively, NF-κB regulates the expression of numerous genes that play a key role in the inflammatory response during human and experimental kidney injury. Multiple stimuli activate NF-κB 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-κB inhibitors tend to reduce inflammation in experimental kidney injury but not always. Although many drugs in current use clinically influence NF-κB activation, there are no data regarding specific NF-κB inhibition in human kidney disease.