LE MAITRE, Christine Lyn, FREEMONT, Anthony J and HOYLAND, Judith Alison (2005). The role of interleukin-1 in the pathogenesis of human intervertebral disc degeneration. Arthritis Research & Therapy, 7 (4), R732-R745.
Le_Maitre_-_The_role_of_interleukin-1_in_the_pathogenesis_of_human_intervertebral_disc_degeneration..pdf - Published Version
Available under License Creative Commons Attribution.
Download (1MB) | Preview
In this study, we investigated the hypotheses that in human intervertebral disc (IVD) degeneration there is local production of the cytokine IL-1, and that this locally produced cytokine can induce the cellular and matrix changes of IVD degeneration. Immunohistochemistry was used to localize five members of the IL-1 family (IL-1alpha, IL-1beta, IL-1Ra (IL-1 receptor antagonist), IL-1RI (IL-1 receptor, type I), and ICE (IL-1beta-converting enzyme)) in non-degenerate and degenerate human IVDs. In addition, cells derived from non-degenerate and degenerate human IVDs were challenged with IL-1 agonists and the response was investigated using real-time PCR for a number of matrix-degrading enzymes, matrix proteins, and members of the IL-1 family. This study has shown that native disc cells from non-degenerate and degenerate discs produced the IL-1 agonists, antagonist, the active receptor, and IL-1beta-converting enzyme. In addition, immunopositivity for these proteins, with the exception of IL-1Ra, increased with severity of degeneration. We have also shown that IL-1 treatment of human IVD cells resulted in increased gene expression for the matrix-degrading enzymes (MMP 3 (matrix metalloproteinase 3), MMP 13 (matrix metalloproteinase 13), and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs)) and a decrease in the gene expression for matrix genes (aggrecan, collagen II, collagen I, and SOX6). In conclusion we have shown that IL-1 is produced in the degenerate IVD. It is synthesized by native disc cells, and treatment of human disc cells with IL-1 induces an imbalance between catabolic and anabolic events, responses that represent the changes seen during disc degeneration. Therefore, inhibiting IL-1 could be an important therapeutic target for preventing and reversing disc degeneration.
|Research Institute, Centre or Group:||Biomolecular Sciences Research Centre|
|Depositing User:||Jamie Young|
|Date Deposited:||01 Jun 2015 09:34|
|Last Modified:||30 Aug 2015 18:30|
Actions (login required)
Downloads per month over past year