Nuclear factor-kappaB as a therapeutic target in critical care medicine.
Nuclear factor-kappaB is a transcriptional factor required for the gene expression of many inflammatory mediators. Nuclear factor-kappaB activation requires removal and degradation of its inhibitor kappaB, an event that occurs after phosphorylation of inhibitor kappaB by a complex of inhibitor kappaB kinases. These events allow nuclear factor-kappaB to translocate into the nucleus, where it binds to kappaB elements and initiates transcription. Inappropriate and prolonged activation of nuclear factor-kappaB has been linked to several diseases associated with inflammatory events, including septic shock, acute respiratory distress syndrome, ischemia, and reperfusion injury. Thus, the key role of nuclear factor-kappaB in regulating inflammation makes this factor a therapeutic target for reducing tissue and organ damage. Regulation and control of nuclear factor-kappaB can be achieved by gene modification strategies or by pharmacologic inhibition of the key components of the cascade that leads to nuclear factor-kappaB activation. The purpose of our review is to describe these novel therapeutic approaches and their potential efficacy.
Zingarelli
Basilia
B
Children's Hospital Medical Center, Division of Critical Care Medicine, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. bzingarelli@chmcc.org
Sheehan
Maeve
M
Wong
Hector R
HR
D003422:Critical Care / Q000379:methods*; D016503:Drug Delivery Systems; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D012769:Shock / Q000188:drug therapy* / Q000276:immunology
D016328:NF-kappa B