Interleukin 1 (IL-1) is a pluripotent cytokine involved in mediating a variety of physiological processes, including induction of cell proliferation upon wound healing. Treatment of quiescent FS-4 human dermal fibroblast cells with IL-1 activates c-myc gene transcription, and nuclear localization of NF-kappa B. Previously, we have noted that the murine c-myc gene contains two functional NF-kappa B sites located at -1101 to -1081 bp (upstream regulatory element [URE]) and +440 to +459 bp (internal regulatory element [IRE]) relative to the P1 promoter. Here we have demonstrated that IL-1 treatment induced binding of NF-kappa B-like proteins (p50/p65) to these c-myc elements. Heterologous promoter-CAT constructs driven by multiple copies of either the URE or IRE were IL-1 inducible when transfected into FS-4 cells. In contrast, constructs harboring elements with two G to C residue conversions, such that they were no longer able to bind NF-kappa B, were not responsive to IL-1. Mutation of these two base pairs at both NF-kappa B sites within a c-myc promoter/exon I-CAT construct, resulted in loss of inducibility with IL-1 upon transfection into quiescent FS-4 cells. Thus, IL-1 significantly induces c-myc expression through positive regulation by NF-kappa B, suggesting a role for this family of factors in activation of proliferation associated with wound healing.
Article|
September 01 1992
NF-kappa B-like factors mediate interleukin 1 induction of c-myc gene transcription in fibroblasts.
D J Kessler,
D J Kessler
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
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M P Duyao,
M P Duyao
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
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D B Spicer,
D B Spicer
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
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G E Sonenshein
G E Sonenshein
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
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D J Kessler
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
M P Duyao
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
D B Spicer
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
G E Sonenshein
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1992) 176 (3): 787–792.
Citation
D J Kessler, M P Duyao, D B Spicer, G E Sonenshein; NF-kappa B-like factors mediate interleukin 1 induction of c-myc gene transcription in fibroblasts.. J Exp Med 1 September 1992; 176 (3): 787–792. doi: https://doi.org/10.1084/jem.176.3.787
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