MYD88-dependent and -independent activation of TREM-1 via specific TLR ligands
MYD88-dependent and -independent activation of TREM-1 via specific TLR ligands
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DOI：
10.1002/eji.200839156
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发表时间：
2010-01-01
影响因子：
5.4
通讯作者：
Sadikot, Ruxana T.
中科院分区：
文献类型：
--
作者：
Zheng, Heng;Heiderscheidt, Caitlin A.;Sadikot, Ruxana T.
髓样细胞表达的触发受体1（TREM - 1）在髓样细胞激活的炎症反应中起重要作用。尽管已表明脂多糖（LPS）和脂磷壁酸等Toll样受体（TLR）配体可上调巨噬细胞和中性粒细胞中TREM - 1的表达，但特定TLR在诱导TREM - 1表达中的作用仍不清楚。在本研究中，我们探讨了TLR的存在对于TREM - 1表达是否是必需的。我们发现来自TLR4和TLR2基因敲除（KO）小鼠的骨髓来源巨噬细胞在其特异性配体刺激下不能诱导TREM - 1的信使核糖核酸（mRNA）和蛋白质表达。有趣的是，在髓样分化因子88（MyD88）基因敲除的巨噬细胞中，LPS诱导的TREM - 1表达未改变，这表明在TLR下游存在一条不依赖MyD88的途径诱导TREM - 1的表达。通过小干扰RNA（siRNA）抑制含Toll/白细胞介素 - 1受体结构域的衔接蛋白诱导干扰素 - β（TRIF）的表达，可降低LPS诱导的TREM - 1表达，这表明LPS诱导的TREM - 1表达是由TRIF信号通路介导的。另一方面，脂磷壁酸诱导的TREM - 1表达依赖于MyD88的表达。这些数据表明，TLR配体诱导的TREM - 1表达继发于下游信号事件，并且TLR的存在对于其特异性配体诱导的TREM - 1表达是必需的。然而，TREM - 1表达所需的下游信号传导取决于刺激物以及启动信号传导的表面受体。
Triggering receptor expressed on myeloid cells (TREM)-1 plays an important role in myeloid cell-activated inflammatory responses. Although TLR ligands such as LPS and lipoteichoic acid have been shown to upregulate TREM-1 expression in macrophage and neutrophils, the role of specific TLR in inducing the expression of TREM-1 remains unclear. In this study, we investigated whether the presence of TLR is necessary for the expression of TREM-1. We show that BM-derived macrophages from TLR4 and TLR2 KO mice failed to induce expression of TREM-1 message and protein in response to their specific ligands. interestingly, the expression of TREM-1 in response to LPS is not altered in myeloid differentiation factor 88 (MyD88) KO macrophages, suggesting that downstream of TLR a MyD88-independent pathway induces the expression of TREM-1. inhibiting toll/IL-1R domain-containing adaptor-inducing IFN-beta (TRIF) expression by siRNA decreased TREM-1 expression in response to LPS, suggesting that the expression of TREM-1 in response to LPS was mediated by the TRIF signaling pathway. On the other hand, the expression of TREM-1 in response to lipoteichoic acid is dependent on MyD88 expression. These data indicate that the expression of TREM-1 in response to TLR ligands occurs secondary to downstream signaling events and that the presence of TLR is necessary for the expression of TREM-1 in response to their specific ligands. However, the downstream signaling required for the expression of TREM-1 is dependent on the stimulus and the surface receptor through which the signaling is initiated.