LAIR-1 shedding from human fibroblast-like synoviocytes in rheumatoid arthritis following TNF-α stimulation
LAIR-1 shedding from human fibroblast-like synoviocytes in rheumatoid arthritis following TNF-α stimulation
复制标题
TNF-α 刺激后类风湿性关节炎中人成纤维细胞样滑膜细胞中 LAIR-1 的脱落
DOI：
10.1111/cei.13100
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发表时间：
2018-05-01
影响因子：
4.6
通讯作者：
Ding, Y.
中科院分区：
文献类型：
--
作者：
Zhang, Y.;Wang, S.;Ding, Y.
本研究通过检测类风湿关节炎（RA）患者成纤维样滑膜细胞（FLS）中抑制性受体白细胞相关免疫球蛋白（IG）样受体1（LAIR-1）的表达，探讨LAIR-1在调节炎性细胞因子、基质金属蛋白酶（MMPs）和滑膜细胞侵袭性中的作用。LAIR-1在RA患者、骨关节炎患者和健康供体的滑膜组织中的表达通过免疫组织化学进行分析。流式细胞术检测膜结合型mLAIR-1。采用定量聚合酶链反应（qPCR）分析FLS中炎症相关因素和MMP活性。LAIR-1在RA患者滑膜中的表达高于骨关节炎患者。Vimentin/LAIR-1免疫共染色显示LAIR-1主要定位于RA患者的FLS。令人惊讶的是，从RA患者分离的原发性FLS具有低水平的mLAIR-1表达，具有胞质分布。LAIR-1的胞外结构域在肿瘤坏死因子（TNF）-α的作用下从细胞表面脱落，这一过程可被丝氨酸蛋白酶抑制剂阻断。另外的实验表明，LAIR-1过表达显著降低了FLS的侵袭，这同时降低了TNF-α存在下白细胞介素（IL）-6，IL-8和MMP-13的mRNA水平。我们的研究表明，LAIR-1是一种抗炎分子，在RA患者的FLS中上调;然而，细胞表面LAIR-1可以从RA炎症微环境中的细胞脱落。这可能会削弱LAIR-1与其配体的相互作用，从而降低LAIR-1的抗炎作用。这些结果表明，LAIR-1可能是一个重要的因素参与调解的进行性关节破坏的RA。
This study examined the expression of the inhibitory receptor, leucocyte-associated immunoglobulin (Ig)-like receptor-1 (LAIR-1) in fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) patients to investigate its potential role in the modulation of inflammatory cytokines, matrix metalloproteinases (MMPs) and invasiveness of synoviocytes. LAIR-1 expression in synovial tissues from RA patients, osteoarthritis patients and healthy donors was analysed by immunohistochemistry. The membrane-bound form (mLAIR-1) was detected by flow cytometry. Factors involved in inflammation and MMP activity in FLS were analysed by quantitative polymerase chain reaction (qPCR). LAIR-1 expression was higher in the synovia of the RA patients than those of the osteoarthritis patients. Co-immunostaining of vimentin/LAIR-1 demonstrated that LAIR-1 was localized mainly in FLS in the RA patients. Surprisingly, primary FLS isolated from the RA patients had low levels of mLAIR-1 expression, with cytoplasmic distribution. The extracellular domain of LAIR-1 was shed from the cell surface in response to tumour necrosis factor (TNF)-alpha, and thisprocess could be blocked by serine protease inhibitors. Additional experiments indicated that LAIR-1 over-expression reduced FLS invasion considerably, which reduced simultaneously the mRNA levels of interleukin (IL)-6, IL-8 and MMP-13 in the presence of TNF-alpha. Our study demonstrated that LAIR-1 is an anti-inflammatory molecule, and was up-regulated in FLS in the RA patients; however, cell-surface LAIR-1 could be shed from cells in the inflammatory microenvironment in RA. This may weaken the interaction of LAIR-1 with its ligand, thus reducing the anti-inflammatory effects of LAIR-1. These findings suggested that LAIR-1 may be an important factor involved in the mediation of the progressive joint destruction in RA.