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

Abstract

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