NF-kappaB in renal inflammation.
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.
Sanz
Ana Belen
AB
Servicio de Nefrologia, Fundación para la Investigación Biomédica del Hospital Universitario La Paz, Madrid, Spain.
Sanchez-Niño
Maria Dolores
MD
Ramos
Adrian Mario
AM
Moreno
Juan Antonio
JA
Santamaria
Beatriz
B
Ruiz-Ortega
Marta
M
Egido
Jesus
J
Ortiz
Alberto
A
D000818:Animals; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D009393:Nephritis / Q000209:etiology*; D014158:Transcription, Genetic
D016328:NF-kappa B