Department of Thoracic and Cardiovascular Surgery, Zhejiang University, Hangzhou, People's Republic of China.
Anesthesiology. 2013 May;118(5):1140-9. doi: 10.1097/ALN.0b013e31828744a5.
Triggering receptor expressed on myeloid cells-1 (TREM-1) can amplify the proinflammatory response and may contribute to the pathogenesis of inflammatory disease such as sepsis. However, the role of TREM-1 in monocyte fate and the detailed molecular mechanisms evoked by TREM-1 are unknown.
Adenoviruses overexpressing TREM-1 were constructed and transfected into a monocytic cell line. After activation of TREM-1 by agonist antibody with or without lipopolysaccharide, apoptosis was induced and assayed using flow cytometry. The signaling pathways downstream of TREM-1 were illustrated by inhibitory experiments. Proapoptotic/antiapoptotic protein levels were measured using immunoblot. In addition, the relationship between the expression levels of TREM-1 in monocytes and the magnitude of monocyte apoptosis were analyzed in septic patients.
Activation of TREM-1 protected monocytes from staurosporine-induced apoptosis. This characteristic was also obtained under lipopolysaccharide stimulation. The protection of TREM-1 against monocyte apoptosis was abrogated after inhibition of extracellular signal-regulated kinase or v-akt murine thymoma viral oncogene homologue signaling. Cross-linking of TREM-1 remarkably up-regulated myeloid cell leukemia-1 protein level, and inhibition of extracellular signal-regulated kinase or v-akt murine thymoma viral oncogene homologue resulted in the reduction of myeloid cell leukemia-1 expression. Inhibition of myeloid cell leukemia-1 abolished the antiapoptotic effect of TREM-1. Furthermore, in septic patients, TREM-1 levels were inversely correlated to the magnitude of apoptosis in monocyte.
TREM-1 played an important role in apoptosis in monocytes. Activation of TREM-1 protected monocytic cells from apoptosis through activation of both extracellular signal-regulated kinase and v-akt murine thymoma viral oncogene homologue pathways and increased expression of myeloid cell leukemia-1 protein. These findings provide a novel additional mechanism for TREM-1-mediated hyperinflammatory response in monocytes.
髓系细胞表达的触发受体-1（TREM-1）可放大促炎反应，并可能有助于炎症性疾病（如败血症）的发病机制。然而，TREM-1 在单核细胞命运中的作用以及 TREM-1 引发的详细分子机制尚不清楚。
构建了过表达 TREM-1 的腺病毒，并转染到单核细胞系中。用激动性抗体（有或没有脂多糖）激活 TREM-1 后，用流式细胞术检测诱导的细胞凋亡。通过抑制实验阐明 TREM-1 下游的信号通路。用免疫印迹法测定促凋亡/抗凋亡蛋白水平。此外，分析了败血症患者单核细胞中 TREM-1 的表达水平与单核细胞凋亡程度之间的关系。
激活 TREM-1 可保护单核细胞免受 staurosporine 诱导的凋亡。在脂多糖刺激下也获得了这一特性。在抑制细胞外信号调节激酶或 v-akt 鼠胸腺瘤病毒癌基因同源物信号后，TREM-1 对单核细胞凋亡的保护作用被消除。TREM-1 的交联显著上调髓样细胞白血病-1 蛋白水平，而细胞外信号调节激酶或 v-akt 鼠胸腺瘤病毒癌基因同源物的抑制导致髓样细胞白血病-1 表达减少。髓样细胞白血病-1 的抑制消除了 TREM-1 的抗凋亡作用。此外，在败血症患者中，TREM-1 水平与单核细胞凋亡程度呈负相关。
TREM-1 在单核细胞凋亡中起重要作用。TREM-1 的激活通过激活细胞外信号调节激酶和 v-akt 鼠胸腺瘤病毒癌基因同源物途径，并增加髓样细胞白血病-1 蛋白的表达，保护单核细胞免于凋亡。这些发现为 TREM-1 介导的单核细胞过度炎症反应提供了一种新的附加机制。
