Tags

Type your tag names separated by a space and hit enter

RETRACTED ARTICLE

Functional NF-IL6/CCAAT enhancer-binding protein is required for tumor necrosis factor alpha-inducible expression of the granulocyte colony-stimulating factor (CSF), but not the granulocyte/macrophage CSF or interleukin 6 gene in human fibroblasts.
J Exp Med. 1995 Feb 01; 181(2):793-8.JE

Abstract

Tumor necrosis factor (TNF) alpha participates in the regulation of the acute-phase, immune, and inflammatory responses. Target genes known to be transcriptionally activated by TNF-alpha include the granulocyte (G)-colony-stimulating factor (CSF) gene, the granulocyte/macrophage (GM)-CSF gene, as well as the interleukin (IL) 6 gene. Functional nuclear factor (NF)-IL6 recognition sites have been identified in regulatory regions of these genes by transient transfection studies using deleted promoter constructs. In addition, NF-IL6 is known to form heterodimeric complexes with the NF-kappa B transcription factor, which is also engaged in the transcriptional regulation of these genes. The indispensable importance of NF-IL6 for regulating gene expression of proinflammatory cytokine genes in response to inflammatory stimuli in vivo remains, however, unclear. We here report, by using both antisense (AS) oligodesoxyribonucleotide (ODN) and ribozyme (RZ)-mediated specific elimination of NF-IL6 transcripts in human fibroblasts, that TNF-alpha-induced synthesis of G-CSF, but not of GM-CSF or IL-6, is abolished in the absence of functional NF-IL6 in vivo. Both AS ODN and RZ targeting of the NF-IL6 transcript eliminate NF-IL6 protein, as shown in Western blot analysis and electrophoretic mobility shift assays. Similarly, fibroblasts exposed to either the AS NF-IL6 ODN or the NF-IL6 RZ, but not to the sense or nonsense ODN or a mutated ribozyme, also failed to respond with functional activation of NF-IL6 as assayed in transient transfection studies using heterologous promoter constructs harboring the NF-IL6 recognition site. In contrast, protein synthesis, DNA-binding activity, and transcriptional activation capacity of the NF-kappa B transcription factor is not impaired upon exposure to either ODN or RZ. Fibroblasts that had been cultured in the presence of the AS NF-IL6 ODN or the NF-IL6RZ failed to synthesize G-CSF protein in response to TNF-alpha, while TNF-alpha-inducible transcription and release of GM-CSF and IL-6 was preserved.

Authors+Show Affiliations

Department of Medical Oncology and Applied Molecular Biology, Universitätsklinikum Rudolf Virchow, Freien Universität Berlin, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Retracted Publication

Language

eng

PubMed ID

7530764

Citation

Kiehntopf, M, et al. "Functional NF-IL6/CCAAT Enhancer-binding Protein Is Required for Tumor Necrosis Factor Alpha-inducible Expression of the Granulocyte Colony-stimulating Factor (CSF), but Not the Granulocyte/macrophage CSF or Interleukin 6 Gene in Human Fibroblasts." The Journal of Experimental Medicine, vol. 181, no. 2, 1995, pp. 793-8.
Kiehntopf M, Herrmann F, Brach MA. Functional NF-IL6/CCAAT enhancer-binding protein is required for tumor necrosis factor alpha-inducible expression of the granulocyte colony-stimulating factor (CSF), but not the granulocyte/macrophage CSF or interleukin 6 gene in human fibroblasts. J Exp Med. 1995;181(2):793-8.
Kiehntopf, M., Herrmann, F., & Brach, M. A. (1995). Functional NF-IL6/CCAAT enhancer-binding protein is required for tumor necrosis factor alpha-inducible expression of the granulocyte colony-stimulating factor (CSF), but not the granulocyte/macrophage CSF or interleukin 6 gene in human fibroblasts. The Journal of Experimental Medicine, 181(2), 793-8.
Kiehntopf M, Herrmann F, Brach MA. Functional NF-IL6/CCAAT Enhancer-binding Protein Is Required for Tumor Necrosis Factor Alpha-inducible Expression of the Granulocyte Colony-stimulating Factor (CSF), but Not the Granulocyte/macrophage CSF or Interleukin 6 Gene in Human Fibroblasts. J Exp Med. 1995 Feb 1;181(2):793-8. PubMed PMID: 7530764.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional NF-IL6/CCAAT enhancer-binding protein is required for tumor necrosis factor alpha-inducible expression of the granulocyte colony-stimulating factor (CSF), but not the granulocyte/macrophage CSF or interleukin 6 gene in human fibroblasts. AU - Kiehntopf,M, AU - Herrmann,F, AU - Brach,M A, PY - 1995/2/1/pubmed PY - 1995/2/1/medline PY - 1995/2/1/entrez SP - 793 EP - 8 JF - The Journal of experimental medicine JO - J Exp Med VL - 181 IS - 2 N2 - Tumor necrosis factor (TNF) alpha participates in the regulation of the acute-phase, immune, and inflammatory responses. Target genes known to be transcriptionally activated by TNF-alpha include the granulocyte (G)-colony-stimulating factor (CSF) gene, the granulocyte/macrophage (GM)-CSF gene, as well as the interleukin (IL) 6 gene. Functional nuclear factor (NF)-IL6 recognition sites have been identified in regulatory regions of these genes by transient transfection studies using deleted promoter constructs. In addition, NF-IL6 is known to form heterodimeric complexes with the NF-kappa B transcription factor, which is also engaged in the transcriptional regulation of these genes. The indispensable importance of NF-IL6 for regulating gene expression of proinflammatory cytokine genes in response to inflammatory stimuli in vivo remains, however, unclear. We here report, by using both antisense (AS) oligodesoxyribonucleotide (ODN) and ribozyme (RZ)-mediated specific elimination of NF-IL6 transcripts in human fibroblasts, that TNF-alpha-induced synthesis of G-CSF, but not of GM-CSF or IL-6, is abolished in the absence of functional NF-IL6 in vivo. Both AS ODN and RZ targeting of the NF-IL6 transcript eliminate NF-IL6 protein, as shown in Western blot analysis and electrophoretic mobility shift assays. Similarly, fibroblasts exposed to either the AS NF-IL6 ODN or the NF-IL6 RZ, but not to the sense or nonsense ODN or a mutated ribozyme, also failed to respond with functional activation of NF-IL6 as assayed in transient transfection studies using heterologous promoter constructs harboring the NF-IL6 recognition site. In contrast, protein synthesis, DNA-binding activity, and transcriptional activation capacity of the NF-kappa B transcription factor is not impaired upon exposure to either ODN or RZ. Fibroblasts that had been cultured in the presence of the AS NF-IL6 ODN or the NF-IL6RZ failed to synthesize G-CSF protein in response to TNF-alpha, while TNF-alpha-inducible transcription and release of GM-CSF and IL-6 was preserved. SN - 0022-1007 UR - https://www.unboundmedicine.com/medline/citation/7530764/Functional_NF_IL6/CCAAT_enhancer_binding_protein_is_required_for_tumor_necrosis_factor_alpha_inducible_expression_of_the_granulocyte_colony_stimulating_factor__CSF__but_not_the_granulocyte/macrophage_CSF_or_interleukin_6_gene_in_human_fibroblasts_ L2 - https://rupress.org/jem/article-lookup/doi/10.1084/jem.181.2.793 DB - PRIME DP - Unbound Medicine ER -