A soluble form of the triggering receptor expressed on myeloid cells-1 modulates the inflammatory response in murine sepsis.
A soluble form of the triggering receptor expressed on myeloid cells-1 modulates the inflammatory response in murine sepsis.
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DOI：
10.1084/jem.20040708
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发表时间：
2004-12-06
影响因子：
15.3
通讯作者：
Faure, GC
中科院分区：
文献类型：
--
作者：
Gibot, S;Kolopp-Sarda, MN;Béné, MC;Bollaert, PE;Lozniewski, A;Mory, F;Levy, B;Faure, GC
关键词：
髓样细胞表达的触发受体（TREM）-1是最近发现的在中性粒细胞和单核细胞亚群的表面上表达的受体。据报道，TREM-1的参与在微生物产物的存在下触发促炎细胞因子的合成。先前，我们已经鉴定了TREM-1的可溶形式（斯特雷姆-1），并且在来自感染性休克患者而非对照的血清样品中观察到显著水平。在这里，我们研究了它在脓毒症炎症调节中的假定作用。我们观察到，斯特雷姆-1分泌的单核细胞在体外激活的LPS和参与感染性休克的实验模型的动物的血清中。在体外和体内，模拟斯特雷姆-1的短的高度保守结构域的合成肽似乎减弱了人单核细胞的细胞因子产生，并保护脓毒症动物免于高反应性和死亡。这种肽似乎不仅在预防而且在下调促炎细胞因子的有害作用方面是有效的。这些数据表明，通过斯特雷姆肽对TREM-1的体内调节可能是用于治疗脓毒症的合适的治疗工具。
The triggering receptor expressed on myeloid cells (TREM)-1 is a recently discovered receptor expressed on the surface of neutrophils and a subset of monocytes. Engagement of TREM-1 has been reported to trigger the synthesis of proinflammatory cytokines in the presence of microbial products. Previously, we have identified a soluble form of TREM-1 (sTREM-1) and observed significant levels in serum samples from septic shock patients but not controls. Here, we investigated its putative role in the modulation of inflammation during sepsis. We observed that sTREM-1 was secreted by monocytes activated in vitro by LPS and in the serum of animals involved in an experimental model of septic shock. Both in vitro and in vivo, a synthetic peptide mimicking a short highly conserved domain of sTREM-1 appeared to attenuate cytokine production by human monocytes and protect septic animals from hyper-responsiveness and death. This peptide seemed to be efficient not only in preventing but also in down-modulating the deleterious effects of proinflammatory cytokines. These data suggest that in vivo modulation of TREM-1 by sTREM peptide might be a suitable therapeutic tool for the treatment of sepsis.
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