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Activation of interleukin-6 gene expression through the NF-κB transcription factor

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.

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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.

Item Type:Article
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URLURL TypeDescription CentralArticle
Baltimore, David0000-0001-8723-8190
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.
Funding AgencyGrant Number
Leukemia Society of AmericaUNSPECIFIED
NIHGM 39458
Issue or Number:5
PubMed Central ID:PMC360580
Record Number:CaltechAUTHORS:20200626-135308824
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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
Deposited By: George Porter
Deposited On:26 Jun 2020 21:27
Last Modified:16 Nov 2021 18:28

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