Activation and regulation of NFkappaB during acute inflammation

During the acute inflammatory response, there is induction of a mediator cascade which functions to activate residential macrophages and recruit blood leukocytes to the site of the inflammatory insult. Dysregulation of this process can cause an exaggerated inflammatory response and lead to tissue injury. Recent studies have focused on the transcription factor NFkappaB, which controls the gene expression of many pro-inflammatory mediators. Under normal conditions, NFkappaB is retained in the cytosol by inhibitory proteins of the IkappaB family. In response to an inflammatory insult, IkappaB proteins are degraded and the free NFkappaB complex translocates to the nucleus where it initiates gene transcription. An understanding of the in vivo mechanisms leading to the activation of NFkappaB, and the regulatory mechanisms that exist to limit this activation, may lead to the development of novel new therapeutic options for inflammatory injury. In this review we will discuss the current knowledge of the role of NFkappaB in the development of acute inflammation, as well as the regulatory mechanisms that exist to prevent the activation of NFkappaB and resolve inflammatory tissue injury.