Department of Veterans Affairs, Jesse Brown VA Hospital, and Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
Eur J Immunol. 2010 Jan;40(1):162-71. doi: 10.1002/eji.200839156.
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.
触发受体表达在髓样细胞 (TREM)-1 在髓样细胞激活炎症反应中发挥重要作用。虽然 TLR 配体，如 LPS 和脂磷壁酸已被证明上调在巨噬细胞和中性粒细胞的 TREM-1 的表达，特定的 TLR 诱导 TREM-1 表达的作用仍不清楚。在这项研究中，我们研究是否存在 TLR 是 TREM-1 表达所必需的。我们表明，从 TLR4 和 TLR2 KO 小鼠骨髓来源的巨噬细胞未能诱导 TREM-1 消息和蛋白质表达对其特定的配体。有趣的是，TREM-1 的表达对 LPS 的反应并没有改变在髓样分化因子 88 (MyD88) KO 巨噬细胞，这表明 TLR 下游的一个 MyD88 独立途径诱导 TREM-1 的表达。通过 siRNA 抑制 toll/IL-1R 域包含衔接诱导 IFN-beta (TRIF) 的表达降低了 LPS 反应中的 TREM-1 表达，表明 TREM-1 的表达 LPS 介导的 TRIF 信号通路。另一方面，TREM-1 的表达对脂磷壁酸的依赖于 MyD88 的表达。这些数据表明，TREM-1 的表达对 TLR 配体发生继发于下游信号事件和 TLR 的存在是必需的 TREM-1 表达对其特定的配体。然而，TREM-1 的表达所需的下游信号取决于刺激和表面受体，通过该信号被启动。
