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