Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.
Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.
Cells. 2021 Sep 21;10(9):2500. doi: 10.3390/cells10092500.
The inflammatory cytokine interleukin-26 (IL-26) is highly expressed in the serum and synovial fluid of patients with inflammatory arthritis. The effect of IL-26 on human articular chondrocytes (HACs) remains unclear. Obesity is associated with disability of patients with rheumatoid arthritis and disease activity in those with ankylosing spondylitis. The saturated free fatty acid palmitate with IL-1β can synergistically induce catabolic effects in HACs. The aim of this study was to evaluate the effects of IL-26 and palmitate in HACs. In this study, palmitate markedly synergizes the IL-26-induced proinflammatory effects and matrix protease, including COX-2, IL-6, and MMP-1, in HACs via the toll-like receptor 4 (TLR4)-ERK1/2-c-Jun signal transduction pathway. The synergistic catabolic effects of palmitate and IL-26 were attenuated by inhibitors of TLR4 (TAK242), ERK1/2 (U0126), or c-Jun (SP600125) in HACs and cartilage matrix. In addition, metformin, a potential inhibitor of TLR4, also decreased expression of COX-2 and IL-6 induced by co-incubation with IL-26 and palmitate. IL-26 and palmitate synergistically induced expression of inflammatory and catabolic mediators, resulting in articular cartilage matrix breakdown. The present study also revealed a possible mechanism and therapeutic targets against articular cartilage degradation by increased saturated fatty acids in patients with inflammatory arthritis.
炎症细胞因子白细胞介素-26（IL-26）在炎症性关节炎患者的血清和滑液中高度表达。IL-26 对人关节软骨细胞（HACs）的影响尚不清楚。肥胖与类风湿关节炎患者的残疾以及强直性脊柱炎患者的疾病活动相关。与 IL-1β 结合的饱和游离脂肪酸棕榈酸可以协同诱导 HACs 的分解代谢作用。本研究旨在评估 IL-26 和棕榈酸对 HACs 的影响。在这项研究中，棕榈酸通过 Toll 样受体 4（TLR4）-ERK1/2-c-Jun 信号转导通路显著协同增强了 IL-26 诱导的 HACs 的促炎作用和基质蛋白酶，包括 COX-2、IL-6 和 MMP-1。TLR4（TAK242）、ERK1/2（U0126）或 c-Jun（SP600125）抑制剂可减弱 HACs 和软骨基质中棕榈酸和 IL-26 的协同分解代谢作用。此外，潜在的 TLR4 抑制剂二甲双胍也降低了与 IL-26 和棕榈酸共孵育诱导的 COX-2 和 IL-6 的表达。IL-26 和棕榈酸协同诱导炎症和分解代谢介质的表达，导致关节软骨基质降解。本研究还揭示了炎症性关节炎患者中增加的饱和脂肪酸可能通过增加炎症细胞因子和饱和游离脂肪酸来破坏关节软骨的机制和治疗靶点。
