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首页> 外文期刊>Infection and immunity >Recognition of Streptococcus pneumoniae and Muramyl Dipeptide by NOD2 Results in Potent Induction of MMP-9, Which Can Be Controlled by Lipopolysaccharide Stimulation
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Recognition of Streptococcus pneumoniae and Muramyl Dipeptide by NOD2 Results in Potent Induction of MMP-9, Which Can Be Controlled by Lipopolysaccharide Stimulation

机译：NOD2识别肺炎链球菌和Muramyl二肽导致强效诱导MMP-9，这可以通过脂多糖刺激来控制。

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Matrix metallopeptidase 9 (MMP-9) is a protease involved in the degradation of extracellular matrix collagen. Evidence suggests that MMP-9 is involved in pathogenesis during Streptococcus pneumoniae infection. However, not much is known about the induction of MMP-9 and the regulatory processes involved. We show here that the Gram-positive bacteria used in this study induced large amounts of MMP-9, in contrast to the Gram-negative bacteria that were used. An important pathogen-associated molecular pattern (PAMP) for Gram-positive bacteria is muramyl dipeptide (MDP). MDP is a very potent inducer of MMP-9 and showed a dose-dependent MMP-9 induction. Experiments using peripheral blood mononuclear cells (PBMCs) from Crohn's disease patients with nonfunctional NOD2 showed that MMP-9 induction by Streptococcus pneumoniae and MDP is NOD2 dependent. Increasing amounts of lipopolysaccharide (LPS), an important PAMP for Gram-negative bacteria, resulted in decreasing amounts of MMP-9. Moreover, the induction of MMP-9 by MDP could be counteracted by simultaneously adding LPS. The inhibition of MMP-9 expression by LPS was found to be regulated posttranscriptionally, independently of tissue inhibitor of metalloproteinase 1 (TIMP-1), an endogenous inhibitor of MMP-9. Collectively, these data show that Streptococcus pneumoniae is able to induce large amounts of MMP-9. These high MMP-9 levels are potentially involved in Streptococcus pneumoniae pathogenesis.
机译：基质金属肽酶9（MMP-9）是一种参与细胞外基质胶原蛋白降解的蛋白酶。有证据表明，MMP-9参与了肺炎链球菌感染期间的发病机理。但是，关于MMP-9的诱导及其涉及的调控过程知之甚少。我们在这里显示，与使用的革兰氏阴性菌相比，本研究中使用的革兰氏阳性菌诱导了大量的MMP-9。革兰氏阳性细菌的一种重要的病原体相关分子模式（PAMP）是穆拉米二肽（MDP）。 MDP是MMP-9的强力诱导剂，并显示出剂量依赖性MMP-9诱导作用。使用来自患有功能性NOD2的克罗恩病患者的外周血单个核细胞（PBMC）进行的实验表明，肺炎链球菌和MDP诱导的MMP-9是NOD2依赖性的。脂多糖（LPS）（对于革兰氏阴性细菌而言很重要的PAMP）的数量增加导致MMP-9数量减少。此外，通过同时添加LPS可以抵消MDP对MMP-9的诱导。发现LPS对MMP-9表达的抑制在转录后受到调控，而与金属蛋白酶1（TIMP-1）的组织抑制剂（MMP-9的内源抑制剂）无关。总的来说，这些数据表明肺炎链球菌能够诱导大量的MMP-9。这些高的MMP-9水平可能与肺炎链球菌的发病机理有关。

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