Interleukin-6 induction by tumor necrosis factor and interleukin-1 in human fibroblasts involves activation of a nuclear factor binding to a kappa B-like sequence.
- 1 July 1990
- journal article
- research article
- Published by Informa UK Limited in Molecular and Cellular Biology
- Vol. 10 (7), 3818-3823
- https://doi.org/10.1128/mcb.10.7.3818
Abstract
Using variable-length deletion constructs of the 5'-flanking region of the human interleukin-6 (IL-6) gene linked to the chloramphenicol acetyltransferase gene, we showed that the region from positions -109 to -50 mediated the bulk of the response to tumor necrosis factor (TNF) or interleukin-1 (IL-1), while it was less responsive to forskolin. DNA mobility shift assays and DNase I footprinting analysis identified a nuclear protein from TNF- or IL-1-treated fibroblasts that bound to a region comprising a kappa B-like element located between positions -72 and -63 on the IL-6 gene. On the basis of these and other experiments, we conclude that TNF and IL-1 apparently activate IL-6 gene expression by closely related mechanisms involving activation of a NF-kappa B-like factor, whereas the pathway of IL-6 induction by forskolin is, in part, different.Keywords
This publication has 36 references indexed in Scilit:
- Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B.Proceedings of the National Academy of Sciences, 1989
- Tumor necrosis factor alpha induces proteins that bind specifically to kappa B-like enhancer elements and regulate interleukin 2 receptor alpha-chain gene expression in primary human T lymphocytes.Proceedings of the National Academy of Sciences of the United States of America, 1989
- Prolonged activation of jun and collagenase genes by tumour necrosis factor-αNature, 1989
- Enhancement of cAMP levels and of protein kinase activity by tumor necrosis factor and interleukin 1 in human fibroblasts: role in the induction of interleukin 6.Proceedings of the National Academy of Sciences of the United States of America, 1988
- Activation of the human "beta 2-interferon/hepatocyte-stimulating factor/interleukin 6" promoter by cytokines, viruses, and second messenger agonists.Proceedings of the National Academy of Sciences of the United States of America, 1988
- Synthesis of interleukin 6 (interferon-beta 2/B cell stimulatory factor 2) in human fibroblasts is triggered by an increase in intracellular cyclic AMP.1988
- Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-κB transcription factorCell, 1988
- Two functional estrogen response elements are located upstream of the major chicken vitellogenin gene.Molecular and Cellular Biology, 1988
- B-cell-stimulatory factor 2 (beta 2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells.Proceedings of the National Academy of Sciences of the United States of America, 1987
- Structure and expression of human B cell stimulatory factor-2 (BSF-2/IL-6) gene.1987