Libermann, Towia A. and Baltimore, David (1990) Activation of interleukin-6 gene expression through the NF-κB transcription factor. Molecular and Cellular Biology, 10 (5). pp. 2327-2334. ISSN 0270-7306. PMCID PMC360580. doi:10.1128/mcb.10.5.2327. https://resolver.caltech.edu/CaltechAUTHORS:20200626-135308824
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Abstract
The promoter region of the interleukin-6 (IL-6) gene has a putative NF-κB-binding site. We found that a fragment of the IL-6 promoter containing the site specifically binds highly purified NF-κB protein and the NF-κB protein in nuclear extracts of phorbol ester-induced Jurkat cells. Mutations of the NF-κB site abolished complex formation with both purified NF-κB 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-κB led to a dramatic increase in CAT activity. Mutations in the NF-κB-binding site abolished inducibility of IL-6 promoter-cat constructs in U-937 cells by lipopolysaccharide, tumor necrosis factor α, 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-κB 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-κB is involved in the control of a variety of genes activated upon inflammation, NF-κB may play a central role in the inflammatory response to infection and tissue injury.
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Alternate Title: | Activation of interleukin-6 gene expression through the NF-kappa B transcription factor | |||||||||
Additional Information: | © 1990 American Society for Microbiology. Received 11 December 1989/Accepted 31 January 1990 We thank Patrick Baeuerle for helpful discussions and the kind gift of affinity-purified NF-κB. This work was supported by a fellowship from the Leukemia Society of America (T.A.L.) and Public Health Service grant GM 39458 to D.B. from the National Institutes of Health. | |||||||||
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Issue or Number: | 5 | |||||||||
PubMed Central ID: | PMC360580 | |||||||||
DOI: | 10.1128/mcb.10.5.2327 | |||||||||
Record Number: | CaltechAUTHORS:20200626-135308824 | |||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20200626-135308824 | |||||||||
Official Citation: | Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. T A Libermann, D Baltimore Molecular and Cellular Biology May 1990, 10 (5) 2327-2334; DOI: 10.1128/MCB.10.5.2327 | |||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | |||||||||
ID Code: | 104096 | |||||||||
Collection: | CaltechAUTHORS | |||||||||
Deposited By: | George Porter | |||||||||
Deposited On: | 26 Jun 2020 21:27 | |||||||||
Last Modified: | 16 Nov 2021 18:28 |
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