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TREM-2 负调控 LPS 介导的大鼠骨髓间充质干细胞炎症反应。

TREM-2 negatively regulates LPS-mediated inflammatory response in rat bone marrow-derived MSCs.

机构信息

Department of Orthopedics, Sun Yat‑sen Memorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.

Department of Orthopedics, Zengcheng People's Hospital of Guangzhou, Guangzhou, Guangdong 511300, P.R. China.

出版信息

Mol Med Rep. 2017 Oct;16(4):4777-4783. doi: 10.3892/mmr.2017.7212. Epub 2017 Aug 10.

Abstract

To the best of our knowledge, our previous study demonstrated the expression of triggering receptor expressed on myeloid cells 2 (TREM‑2) in human bone marrow mesenchymal stem cells (MSCs) for the first time. However, the inflammation regulatory role of TREM‑2 in MSCs remain elusive. The aim of the present study was to investigate the immune regulation and the underlying mechanism of TREM‑2 in rat bone marrow MSCs. MSCs were divided into three groups: NullMSCs, TREM‑2MSCs, and NormMSCs. TREM‑2 was expressed in MSCs at the mRNA and protein level. Following stimulation by lipopolysaccharide (LPS), the gene transcription levels of TREM‑2 and inflammatory cytokines were increased. The expression levels of inflammatory cytokines, including tumor necrosis factor‑α (TNF‑α) and interleukin‑1β (IL‑1β), in the TREM‑2MSCs lentiviral vector group were significantly downregulated, and the expression of IL‑10 was significantly upregulated compared with the controls. Western blot analysis revealed that TREM‑2 downregulated the LPS‑induced inflammatory response in MSCs, which was probably associated with regulating AKT serine/threonine kinase and p38 mitogen‑activated protein kinase downstream signaling proteins. The results of the current study demonstrated that TREM‑2 negatively regulates the LPS‑mediated inflammatory response in MSCs suggesting that TREM‑2 is a potential target of immune regulation in rat MSCs.

摘要

据我们所知,我们之前的研究首次表明触发受体表达在髓样细胞 2(TREM-2)在人骨髓间充质干细胞(MSCs)中的表达。然而,TREM-2 在 MSCs 中的炎症调节作用仍不清楚。本研究旨在探讨 TREM-2 在大鼠骨髓间充质干细胞中的免疫调节作用及其潜在机制。MSCs 分为三组:NullMSCs、TREM-2MSCs 和 NormMSCs。TREM-2 在 MSCs 中的 mRNA 和蛋白水平均有表达。在脂多糖(LPS)刺激后,TREM-2 和炎症细胞因子的基因转录水平增加。TREM-2 慢病毒载体组的炎症细胞因子,包括肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的表达水平显著下调,IL-10 的表达水平显著上调。Western blot 分析表明,TREM-2 下调了 LPS 诱导的 MSCs 炎症反应,这可能与调节 AKT 丝氨酸/苏氨酸激酶和 p38 丝裂原活化蛋白激酶下游信号蛋白有关。本研究结果表明,TREM-2 负调控 LPS 介导的 MSCs 炎症反应,提示 TREM-2 是大鼠 MSCs 免疫调节的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2103/5647029/2c6733f0a172/MMR-16-04-4777-g00.jpg

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