Nuclear Factor-κ B Repression in Antiinflammation and Immunosuppression by Glucocorticoids

The transcription factor nuclear factor-kappaB (NF-kappaB) directs transcription of a large number of key molecules in immunological and inflammatory responses. The recently discovered inhibition of transcriptional activity of this factor by the activated glucocorticoid receptor (GR) provides a molecular basis for the potent antiinflammatory and immunosuppressive properties of glucocorticoids. This repressive activity of the GR can function independently of transcriptional activity. Because it has been shown that certain steroid receptor ligands can differentially address transactivation and transrepression functions, it may be possible to develop ligands that specifically suppress NF-kappaB activity and, as a result, are more efficient in treatment of a variety of important chronic inflammatory diseases with less severe side effects than those of currently available drugs.