NF-kappaB in renal inflammation

• Published in: Journal of the American Society of Nephrology 2010-08, Vol.21 (8), p.1254-1262
• Main Authors: Sanz, Ana Belen, Sanchez-Niño, Maria Dolores, Ramos, Adrian Mario, Moreno, Juan Antonio, Santamaria, Beatriz, Ruiz-Ortega, Marta, Egido, Jesus, Ortiz, Alberto
• Format: Article
• Language: English
• Subjects: Animals; Humans; Nephritis - etiology; NF-kappa B - genetics; NF-kappa B - physiology; Transcription, Genetic
• ISSN: 1533-3450
• DOI: 10.1681/ASN.2010020218

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