ANGPTL2 Induces Synovial Inflammation via LILRB2
ANGPTL2 Induces Synovial Inflammation via LILRB2
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DOI：
10.1007/s10753-020-01406-7
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发表时间：
2021-02-04
期刊：
影响因子：
5.1
通讯作者：
Tanimoto, Kotaro
中科院分区：
文献类型：
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作者：
Nishiyama, Sayuri;Hirose, Naoto;Tanimoto, Kotaro
血管生成素样蛋白（ANGPTL）是在各种细胞和组织中表达的循环蛋白，被认为参与受损组织的修复和重塑；然而，ANGPTL2 功能亢进已被证明会引起慢性炎症，从而导致各种疾病的进展。已知 ANGPTL2 通过整合素 α 5 β 1 和白细胞免疫球蛋白样受体亚家族 B 成员 2 (LILRB2) 等受体发挥细胞作用；然而，它们在 ANGPTL2 诱导的炎症中的作用仍不清楚。在这项研究中，我们研究了 ANGPTL2 诱导的炎症机制，涉及 LILRB2 和人成纤维样滑膜细胞 (HFLS) 中的各种信号通路。使用实时 RT-PCR 检查 ANGPTL2 和抗 LILRB2 抗体对各种炎症相关因子基因表达的影响，同时通过蛋白质印迹分析它们对 MAPK、NF-kappa B 和 Akt 磷酸化的影响。我们发现添加ANGPTL2增强了炎症因子的基因表达，而用抗LILRB2抗体预处理12小时降低了这些因子的表达。类似地，添加 ANGPTL2 可激活 HFLS 中 ERK、p38、JNK、NF-kappa B 和 Akt 的磷酸化；然而，这种效应被抗 LILRB2 抗体预处理显着抑制。总之，本研究的结果表明 ANGPTL2 通过 LILRB2 在滑膜细胞中诱导炎症因子的表达。因此，LILRB2可能成为治疗骨关节炎基质降解的潜在治疗剂。
Angiopoietin-like proteins (ANGPTLs) are circulating proteins that are expressed in various cells and tissues and are thought to be involved in the repair and remodeling of damaged tissues; however, ANGPTL2 hyperfunction has been shown to cause chronic inflammation, leading to the progression of various diseases. ANGPTL2 is known to exert cellular effects via receptors such as integrin alpha 5 beta 1 and leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2); however, their roles in ANGPTL2-induced inflammation remain unclear. In this study, we investigated the mechanisms underlying ANGPTL2-induced inflammation involving LILRB2 and various signaling pathways in human fibroblast-like synoviocytes (HFLS). The effects of ANGPTL2 and an anti-LILRB2 antibody on the gene expression of various inflammation-related factors were examined using real-time RT-PCR, while their effects on MAPK, NF-kappa B, and Akt phosphorylation were analyzed by western blotting. We found that the addition of ANGPTL2 enhanced the gene expression of inflammatory factors, whereas pretreatment with the anti-LILRB2 antibody for 12 h decreased the expression of these factors. Similarly, ANGPTL2 addition activated the phosphorylation of ERK, p38, JNK, NF-kappa B, and Akt in HFLS; however, this effect was significantly inhibited by pretreatment with the anti-LILRB2 antibody. Together, the findings of this study demonstrate that ANGPTL2 induces the expression of inflammatory factors via LILRB2 in synovial cells. Therefore, LILRB2 could be a potential therapeutic agent for treating matrix degradation in osteoarthritis.