A Negative Regulatory Region Containing a Glucocorticosteroid Response Element (nGRE) in the Human Interleukin-1β Gene
- 1 February 1997
- journal article
- research article
- Published by Mary Ann Liebert Inc in DNA and Cell Biology
- Vol. 16 (2) , 145-152
- https://doi.org/10.1089/dna.1997.16.145
Abstract
Interleukin-1 beta (IL-1β) is one of the most important inflammatory mediators in human inflammatory and immunological diseases. The regulation of human IL-1β gene expression has been studied for several years, and a few regulatory elements have been discovered in the promoter region. However, little is known about negative regulation of IL-1β expression at the transcriptional level, which may play an important role in anti-inflammatory and immunosuppressive effects. We have identified a negative regulatory element located in the region between -685 and -395. Within this region, a 19-bp nuclear factor binding site (-570 to -552) was characterized by DNase I footprinting and electromobility shift assay. A consensus sequence for a negative glucocorticoid response element (nGRE) and a transcription activator protein-2 binding site were noted within this footprint. Functional studies showed a 2.5-fold increase in promoter activity when this 19-bp binding site was deleted in the reporter constructs IL-1βCAT and IL-1β/SV40 promoter/CAT. Dexamethasone (10-8M) repressed chloramphenicol acetyltransferase (CAT) production by 75% in the wild-type fragment but not in a deletion mutant lacking the 19-bp site. A protein of about 150 kD that bound to this negative regulatory sequence was identified by UV cross-linking. This is the first description of a negative regulatory region responsive to glucocorticoids in a cytokine gene.Keywords
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