Department of Veterans Affairs, Jesse Brown VA Hospital, University of Illinois at Chicago, Chicago, IL, USA.
Exp Cell Res. 2010 Nov 15;316(19):3140-9. doi: 10.1016/j.yexcr.2010.08.009. Epub 2010 Aug 24.
TREM-1 is a superimmunoglobulin receptor present on neutrophils and monocytes, which plays an important role in the amplification of inflammation. The natural ligands for TREM-1 have not been identified; however, Toll-like receptor ligands are known to induce the expression of TREM-1. Blockade of TREM-1 has shown to improve survival in animal models of sepsis. In the present studies, we investigated the role of lipid mediators in the expression of TREM-1. In a macrophage cell line, we show that the expression of TREM-1 in response to LPS and bacteria Pseudomonas aeruginosa is inhibited by PGD(2) and cyclopentanone prostaglandins PGJ(2) and 15-dPGJ(2). The inhibition of TREM-1 by these prostaglandins is independent of the PGD(2) receptors and PPARγ but occurs by activation of Nrf2 and inhibition of NF-κB. Our data suggest a novel mechanism by which these prostaglandins exhibit anti-inflammatory effects and a new therapeutic approach to inhibition of TREM-1.
TREM-1 是一种存在于中性粒细胞和单核细胞上的超免疫球蛋白受体，在炎症放大中发挥重要作用。TREM-1 的天然配体尚未确定；然而，已知 Toll 样受体配体可诱导 TREM-1 的表达。阻断 TREM-1 已被证明可提高脓毒症动物模型的存活率。在本研究中，我们研究了脂质介质在 TREM-1 表达中的作用。在巨噬细胞系中，我们表明脂多糖和铜绿假单胞菌细菌刺激后 TREM-1 的表达被 PGD（2）和环戊酮前列腺素 PGJ（2）和 15-dPGJ（2）抑制。这些前列腺素对 TREM-1 的抑制作用不依赖于 PGD（2）受体和 PPARγ，而是通过 Nrf2 的激活和 NF-κB 的抑制发生的。我们的数据表明，这些前列腺素具有抗炎作用的新机制，以及抑制 TREM-1 的新治疗方法。
