Activation of Interleukin-6 Gene Expression through the NF-κB Transcription Factor
| Autor: | Libermann, T A, Baltimore, D |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Transcriptional Activation
Base Sequence Interleukin-6 DNA Mutational Analysis Molecular Sequence Data Restriction Mapping NF-kappa B Cell Biology Regulatory Sequences Nucleic Acid Cell Line DNA-Binding Proteins Gene Expression Regulation Humans Tetradecanoylphorbol Acetate Amino Acid Sequence Promoter Regions Genetic Molecular Biology Research Article Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 10:2327-2334 |
| ISSN: | 1098-5549 |
| Popis: | The promoter region of the interleukin-6 (IL-6) gene has a putative NF-kappa B-binding site. We found that a fragment of the IL-6 promoter containing the site specifically binds highly purified NF-kappa B protein and the NF-kappa B protein in nuclear extracts of phorbol ester-induced Jurkat cells. Mutations of the NF-kappa B site abolished complex formation with both purified NF-kappa B and the nuclear extract protein. Transient expression of chloramphenicol acetyltransferase (CAT) plasmids containing the IL-6 promoter revealed very little activity of the promoter in U-937 monocytic cells and in HeLa cells before stimulation. However, stimulation of U-937 and HeLa cells by inducers of NF-kappa B led to a dramatic increase in CAT activity. Mutations in the NF-kappa B-binding site abolished inducibility of IL-6 promoter-cat constructs in U-937 cells by lipopolysaccharide, tumor necrosis factor alpha, the double-stranded RNA poly(IC), or phytohemagglutinin and in HeLa cells by tumor necrosis factor alpha and drastically reduced but did not completely eliminate inducibility in HeLa cells stimulated by double-stranded RNA poly(IC) or phorbol 12-myristate 13-acetate. These results suggest that NF-kappa B is an important mediator for activation of the IL-6 gene by a variety of IL-6 inducers in both U-937 and HeLa cells and that alternative inducible enhancer elements contribute in a cell-specific manner to IL-6 gene induction. Because NF-kappa B is involved in the control of a variety of genes activated upon inflammation, NF-kappa B may play a central role in the inflammatory response to infection and tissue injury. |
| Databáze: | OpenAIRE |
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