The NFkappaBb/IkappaB system in acute inflammation.

Abstract

The transcription factor NFkappaB is a primary regulator of a wide variety of proinflammatory mediators. Under normal conditions, NFkappaB is retained in the cytoplasm bound to inhibitory proteins of the IkappaB family. Following cell activation, a number of signal transduction pathways lead to degradation of IkappaB proteins which results in nuclear translocation of NFkappaB and the ensuing transcriptional activation of proinflammatory genes. Several endogenous regulatory mediators, which function to prevent uncontrolled inflammation, exert their effects by blocking the activation of NFkappaB. Thus, NFkappaB appears to be at the heart of the acute inflammatory response. The present review discusses the role of NFkappaB in the induction and propagation of the acute inflammatory response as well as the regulation and resolution of this process.