Ornatowska M, Azim A C, Wang X, Christman J W, Xiao L, Joo M, Sadikot R T
Section of Pulmonary, Critical Care, and Sleep Medicine, University of Illinois, Chicago, IL 60612, USA.
Am J Physiol Lung Cell Mol Physiol. 2007 Dec;293(6):L1377-84. doi: 10.1152/ajplung.00140.2007. Epub 2007 Sep 28.
Triggering receptor expressed on myeloid cells 1 (TREM-1) is a recently discovered molecule that is expressed on the cell surface of monocytes and neutrophils. Engagement of TREM-1 triggers synthesis of proinflammatory cytokines in response to microbes, but the extent and mechanism by which TREM-1 modulates the inflammatory response is poorly defined. In the present study, we investigated the functional effects of blocking TREM-1 on the Toll-like receptor (TLR)4-mediated signaling pathway in macrophages. By transfecting cells with small hairpin interfering RNA molecules to TREM-1 (shRNA), we confirmed that TREM-1 mRNA and protein expression was greatly attenuated in RAW cells in response to treatment with LPS. PCR array for genes related to or activated by the TLR pathway revealed that although the expression of TLR4 itself was not significantly altered by silencing of TREM-1, expression of several genes, including MyD88, CD14, IkappaBalpha, IL-1beta, MCP-1, and IL-10 was significantly attenuated in the TREM-1 knockdown cells in response to treatment with LPS. These data indicate that expression of TREM-1 modulates the TLR signaling in macrophages by altering the expression of both adaptor and effector proteins that are critical to the endotoxin response.
髓系细胞触发受体1（TREM-1）是最近发现的一种分子，表达于单核细胞和中性粒细胞的细胞表面。TREM-1的激活可触发针对微生物的促炎细胞因子合成，但TREM-1调节炎症反应的程度和机制尚不清楚。在本研究中，我们研究了阻断TREM-1对巨噬细胞中Toll样受体（TLR）4介导的信号通路的功能影响。通过用针对TREM-1的小发夹干扰RNA分子（shRNA）转染细胞，我们证实，在用LPS处理后，RAW细胞中TREM-1的mRNA和蛋白表达显著减弱。针对与TLR途径相关或由其激活的基因的PCR阵列显示，虽然沉默TREM-1不会显著改变TLR4本身的表达，但在用LPS处理后，TREM-1敲低细胞中包括MyD88、CD14、IkappaBalpha、IL-1β、MCP-1和IL-10在内的几个基因的表达显著减弱。这些数据表明，TREM-1的表达通过改变对内毒素反应至关重要的衔接蛋白和效应蛋白的表达来调节巨噬细胞中的TLR信号传导。
