Department of Biochemical, Physiological and Nutritional Sciences, School of Medicine, University of Messina, Policlinico Universitario, Messina, Italy.
Innate Immun. 2012 Oct;18(5):675-84. doi: 10.1177/1753425911435953. Epub 2012 Jan 25.
Hyaluronan (HA) oligosaccharides stimulate pro-inflammatory responses in different cell types by modulating both cluster determinant 44 (CD44) and TLR4. The activation of these receptors is also mediated by collagen-induced arthritis (CIA) that, via two different pathways, culminates in the liberation of NF-κB. This then stimulates the production of pro-inflammatory cytokines, including IL-18 and IL-33, that are greatly involved in rheumatoid arthritis. The aim of this study was to investigate the effects of 6-mer HA oligosaccharides on mouse synovial fibroblasts obtained from normal DBA/J1 mice or mice subjected to CIA. Compared with normal synovial fibroblasts (NSF), rheumatoid arthritis synovial fibroblasts (RASF) showed no up-regulation of CD44 and TLR4 mRNA expression and the related proteins, as well as no activation of NF-κB. Very low levels of both mRNA and related proteins were also detected for IL-18 and IL-33. Treatment of NSF and RASF with 6-mer HA oligosaccharides significantly increased all the parameters in both fibroblast groups, although to a greater extent in RASF. The addition of hyaluronan binding protein to both NSF and RASF inhibited HA activity and was able to reduce the effects of 6-mer HA oligosaccharides and the consequent inflammatory response.
透明质酸（HA）寡糖通过调节细胞表面黏附分子 CD44 和 Toll 样受体 4（TLR4）来刺激不同细胞类型的促炎反应。这些受体的激活也受胶原诱导性关节炎（CIA）的影响，通过两条不同的途径，最终导致 NF-κB 的释放。NF-κB 刺激促炎细胞因子的产生，包括白细胞介素 18（IL-18）和白细胞介素 33（IL-33），它们在类风湿关节炎中起着重要作用。本研究旨在探讨 6 -merHA 寡糖对正常 DBA/J1 小鼠或 CIA 小鼠滑膜成纤维细胞的影响。与正常滑膜成纤维细胞（NSF）相比，类风湿关节炎滑膜成纤维细胞（RASF）的 CD44 和 TLR4mRNA 表达及其相关蛋白无上调，NF-κB 也无激活。IL-18 和 IL-33 的 mRNA 和相关蛋白水平也非常低。6-merHA 寡糖处理 NSF 和 RASF 后，两组成纤维细胞的所有参数均显著增加，但在 RASF 中增加幅度更大。透明质酸结合蛋白添加到 NSF 和 RASF 中可抑制 HA 活性，并能降低 6-merHA 寡糖的作用及其引起的炎症反应。
