Glucocorticoid effects on NF-kappaB 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-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.
Liden
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J
Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital, Novum F60, Huddinge, S-141 86, Sweden. Johan.Liden@mednut.ki.se
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Truss
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Gustafsson
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D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D018983:DNA Footprinting; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D020298:U937 Cells
D017931:DNA Primers; D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011965:Receptors, Glucocorticoid; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha