IL-20 may contribute to the pathogenesis of human intervertebral disc herniation

Study Design.: The gene expression of interleukin (IL)-20 on human herniated intervertebral disc. Objective.: To elucidate the role of novel cytokine IL-20 in the pathogenesis of human intervertebral disc (IVD) herniation. Summary of background data.: IL-20 is involved in inflammatory diseases such as psoriasis, atherosclerosis, and rheumatoid arthritis, etc. However, IL-20 is never reported to be associated with the pathogenesis of human disc herniation. Methods.: Twenty consecutive patients who were diagnosed with IVD herniation and received open discectomy were included in this study. The retrieved disc material specimens and the isolated primarily cultured disc cells were immunohistochemically stained to detect the expression of IL-20 and its receptor subunits (IL-20R1, IL-20R2, and IL-22R1). Besides, to investigate the in vitro response of IL-20 on human herniated intervertebral disc, we analyzed the effects of IL-20 alone, in combination with IL-1β, and IL-1β alone on the gene expression and protein levels of various cytokines, chemokines, matrix metalloproteinases (MMPs), etc. Results.: IL-20 and its receptors were detectable in human herniated disc tissues and isolated disc cells. In vitro, IL-1β induced the expression of IL-20. Furthermore, IL-20 induced transcripts of IL-1β, IL-6, vascular endothelial growth factor (VEGF), MMP-3, and monocyte chemoattractant protein (MCP-1) on primarily cultured human disc cells. IL-1β induced transcripts of IL-1β, IL-6, IL-8, VEGF, MMP3, and MCP-1. IL-20 combined with IL-1β induced transcripts of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, IL-8, MMP-3, and MCP-1 to a level higher than those found in cells treated with IL-20 or IL-1β alone.Enzyme-linked immunosorbent assay, analysis also showed that IL-20 combined with IL-1β up-regulated the secretion of TNF-α, IL-6, IL-8, and MCP-1. Conclusion.: IL-20 induces proinflammatory, chemotaxtic, and matrix degradative responses in IVD cells especially in combination with IL-1β. Our study suggests that IL-20 plays an important role in the pathogenesis of disc herniation.