Epigallocatechin 3-gallate suppresses interleukin-1β-induced inflammatory responses in intervertebral disc cellsin vitroand reduces radiculopathic pain in rats
1 Department of Health Science and Technology, ETH Zurich, Switzerland
2 Department of Orthopaedic Surgery, Fukushima Medical University, Fukushima, Japan
3 Balgrist University Hospital, Zurich, Switzerland
4 Department of Neurosurgery, Clinic St. Anna, Lucerne, Switzerland
5 Competence Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Zurich, Switzerland
Abstract
Intervertebral disc (IVD) disease, which is characterised by age-related changes in the adult disc, is the most common cause of disc failure and low back pain. The purpose of this study was to analyse the potential of the biologically active polyphenol epigallocatechin 3-gallate (EGCG) for the treatment of painful IVD disease by identifying and explaining its anti-inflammatory and anti-catabolic activity. Human IVD cells were isolated from patients undergoing surgery due to degenerative disc disease (n= 34) and cultured in 2D or 3D. An inflammatory response was activated by IL-1β, EGCG was added, and the expression/activity of inflammatory mediators and pathways was measured by qRT-PCR, western blotting, ELISA, immunofluorescence and transcription factor assay. The small molecule inhibitor SB203580 was used to investigate the involvement of the p38 pathway in the observed effects. The analgesic properties of EGCG were analysed by the von Frey filament test in Sprague-Dawley rats (n= 60). EGCG significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinasesin vitro, as well as radiculopathic painin vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-κB.
Keywords
- Epigallocatechin 3-gallate
- intervertebral disc degeneration
- low back pain
- IRAK-1
- p38
- NF-κB
- inflammation
- radiculopathy
- EGCG
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