Glucocorticoid effects on NF-κB binding in the transcription of the ICAM-1 gene

Glucocorticoid hormones are potent antiinflammatory drugs. A key mechanism in the antiinflammatory action is repression of the nuclear factor kappa B (NF-kappa B) Signaling pathway. This results in transcriptional repression of inflammatory genes controlled by NF-kappa B, including the intercellular adhesion molecule-1 (ICAM-1), We have investigated expression levels, nuclear translocation and DNA binding of NF-kappa B in vitro and in vivo in U937 cells during activation and repression. Repression of NF-kappa B signaling by glucocorticoids does not prevent NF-kappa B translocation or DNA binding, However interestingly, in vivo foot printing of the NF-kappa B site in the ICAM-1 gene indicates that glucocorticoids change the conformation of the protein complex binding to the NF-kappa B site. These results suggests that NF-kappa B interaction with the glucocorticoid receptor does not displace NF-kappa B from its DNA binding site but rather changes the complex into a transcriptionally inert form. (C) 2000 Academic Press.