1. Interleukin 1 induces hypoxia-inducible factor 1 in human gingival and synovial fibroblasts.
- Author
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Thornton RD, Lane P, Borghaei RC, Pease EA, Caro J, and Mochan E
- Subjects
- Base Sequence, Cells, Cultured, DNA Primers, DNA, Complementary, DNA-Binding Proteins genetics, Gingiva cytology, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Lipopolysaccharides pharmacology, Nuclear Proteins genetics, RNA, Messenger genetics, Synovial Membrane cytology, Tumor Necrosis Factor-alpha pharmacology, DNA-Binding Proteins biosynthesis, Gingiva metabolism, Interleukin-1 physiology, Nuclear Proteins biosynthesis, Synovial Membrane metabolism, Transcription Factors
- Abstract
Rheumatoid arthritis and periodontitis are inflammatory diseases modulated by proinflammatory cytokines [e.g. interleukin (IL-1) 1 and tumour necrosis factor alpha], which activate local fibroblasts to do the following: (1) proliferate, (2) induce gene expression and (3) produce destructive metalloproteinases. Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor (composed of HIF-1alpha and HIF-1beta/aryl hydrocarbon receptor nuclear transporter) that is modulated by hypoxia. HIF-1 binds to and induces several genes containing an HIF-1 consensus-binding site, including vascular endothelial growth factor and several glycolytic enzymes. Through differential screening of a human synovial fibroblast cDNA library, we identified HIF-1alpha as a clone up-regulated by IL-1. The mRNA for HIF-1alpha subunit was increased 3-4-fold by Northern blot analysis after cells had been incubated for 3 h in the presence of IL-1. In addition, IL-1 increased the binding of the heterodimer HIF-1 to the HIF consensus sequence. These results suggest that HIF-1 might have a role in inflammation, possibly in attempting to re-establish homoeostasis.
- Published
- 2000