The roles of IL-19 and IL-20 in the inflammation of degenerative lumbar spondylolisthesis

Kuo-Yuan Huang; Yu-Hsiang Hsu; Wei-Yu Chen; Hui-Ling Tsai; Jing-Jou Yan; Jung-Der Wang; Wen-Lung Liu; Ruey-Mo Lin

doi:10.1186/s12950-018-0195-6

The roles of IL-19 and IL-20 in the inflammation of degenerative lumbar spondylolisthesis

J Inflamm (Lond). 2018 Sep 18:15:19. doi: 10.1186/s12950-018-0195-6. eCollection 2018.

Authors

Kuo-Yuan Huang^{1

2}, Yu-Hsiang Hsu^{2

3}, Wei-Yu Chen⁴, Hui-Ling Tsai¹, Jing-Jou Yan⁵, Jung-Der Wang⁶, Wen-Lung Liu¹, Ruey-Mo Lin⁷

Affiliations

¹ 1Department of Orthopedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
² 2Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
³ 3Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁴ 4Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung, Memorial Hospital, Kaohsiung, Taiwan.
⁵ 5Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁶ 6Department of Public of Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
⁷ 7Department of Orthopedics, Tainan Municipal An-Nan Hospital-China Medical University, Tainan, Taiwan.

Abstract

Background: Degenerative lumbar spondylolisthesis (DLS) is a major cause of spinal canal stenosis and is often related to lower back pain. IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory bone disorders likes intervertebral disc herniation, rheumatoid arthritis (RA), osteoporosis, and bone fracture. IL-19 also acts as a proinflammatory cytokine in RA. The aim of the present study was to investigate whether IL-19 and IL-20 are involved in DLS and compare three different tissues including disc, facet joint, and ligamentum flavum of patients with DLS to verify which tissue is affected more by inflammation.

Methods: Disc, facet joint and ligamentum flavum from 13 patients with DLS was retrieved, and the expression pattern of IL-19, IL-20, IL-20R1, IL-20R2, TNF-α, IL-1β, and MCP-1 was evaluated using immunohistochemical staining with specific antibodies. The disc cells were isolated and incubated with IL-19 and IL-20 under CoCl₂-mimicked hypoxic conditions to analyze the proinflammatory cytokine expression pattern using real-time quantitative PCR with specific primers.

Results: IL-19 and IL-20 were positively stained and accompanied by abundant expression of TNF-α, IL-1β, and MCP-1 in facet joints of DLS patients. IL-19 and IL-20's receptors (IL-20R1 and IL-20R2) were expressed on chondrocytes and fibrocytes/fibroblasts in facet joint and ligamentum flavum tissues from patients with DLS. There was a significant correlation between the expression of IL-20 and IL-1β in facet joint. In vitro assay, IL-19 and IL-20 upregulated the expression of IL-1β, IL-6, TNF-α, IL-8, VEGF, and MCP-1 in primary cultured DLS disc cells under CoCl₂-mimicked hypoxic conditions.

Conclusions: IL-19, IL-20, and their receptors as well as proinflammatory cytokines (TNF-α, IL-1β, and MCP-1) were expressed more in facet joints than the other tissues in patients with DLS; therefore, the etiology of inflammation might be more facet-centric. IL-19 and IL-20 induced proinflammatory cytokine expression in disc cells and might play a role in the pathogenesis of DLS.

Keywords: Degenerative lumbar Spondylolisthesis; IL-19; IL-20; Inflammation.