NF-kappaB activation.
Binding sites for the transcriptional regulatory factor nuclear factor kappa B (NF-kappaB) are present in the promoter regions of many of the proinflammatory cytokines and immunoregulatory mediators important in inducing acute inflammatory responses associated with critical illnesses. Because increased activation of NF-kappaB leads to enhanced expression of these proinflammatory mediators, NF-kappaB activation may be a central event in the development of multiple organ dysfunction associated with infection, blood loss, and ischemia-reperfusion injury. NF-kappaB is normally retained in the cytoplasm through its association with the inhibitory molecule I kappaB. Phosphorylation, ubiquination, and proteolysis of I kappaB allows NF-kappaB to translocate to the nucleus and induce transcription, once associated with the transcriptional cofactor CBP. The transcriptional activity of NF-kappaB can be regulated at multiple steps, including the amount of I kappaB present, NF-kappaB subunit composition, and competition for CBP binding. Because of the central role that NF-kappaB occupies in modulating immunoregulatory responses, further understanding of its regulation will be important in designing future therapies able to prevent or minimize acute inflammatory injury associated with critical illness.
Abraham
E
E
Department of Medicine, University of Colorado Health Sciences Center, Denver, USA.
D000201:Activation Analysis; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D018390:Gene Targeting; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D016207:Cytokines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014157:Transcription Factors