MMP-8 deficiency increases TLR/RAGE ligands S100A8 and S100A9 and exacerbates lung inflammation during endotoxemia.
MMP-8 deficiency increases TLR/RAGE ligands S100A8 and S100A9 and exacerbates lung inflammation during endotoxemia.
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DOI：
10.1371/journal.pone.0039940
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Albaiceta GM
中科院分区：
文献类型：
--
作者：
González-López A;Aguirre A;López-Alonso I;Amado L;Astudillo A;Fernández-García MS;Suárez MF;Batalla-Solís E;Colado E;Albaiceta GM
基质金属蛋白酶-8主要由中性粒细胞释放，通过其切割多种介质的能力是炎症反应的关键调节剂。在此，我们报告了一个内毒素血症模型的结果后，腹腔内注射LPS缺乏MMP-8和野生型对应的小鼠。对照组、生理盐水处理组动物在基因型之间无差异。然而，有一个增加的肺部炎症反应，与一个突出的嗜中性粒细胞浸润的突变动物LPS治疗后。使用蛋白质组学方法，我们将alarmins S100 A8和S100 A9确定为基因型之间的两个主要差异。缺乏MMP-8的小鼠在肺匀浆中表现出这两种分子的显著增加，但在脾和血清中没有。缺乏MMP-8的小鼠也显示MIP-1α水平增加和非经典NF-κB通路的显著激活，而CXC趋化因子如MIP-2或LIX无差异。这些结果表明，MMP-8可以调节S100 A8和S100 A9的水平，并且MMP-8的缺失促进了内毒素血症期间的肺部炎症反应。
Matrix metalloproteinase-8, released mainly from neutrophils, is a critical regulator of the inflammatory response by its ability to cleave multiple mediators. Herein, we report the results of a model of endotoxemia after intraperitoneal LPS injection in mice lacking MMP-8 and their wildtype counterparts. Control, saline-treated animals showed no differences between genotypes. However, there was an increased lung inflammatory response, with a prominent neutrophilic infiltration in mutant animals after LPS treatment. Using a proteomic approach, we identify alarmins S100A8 and S100A9 as two of the main differences between genotypes. Mice lacking MMP-8 showed a significant increase in these two molecules in lung homogenates, but not in spleen and serum. Mice lacking MMP-8 also showed an increase in MIP-1α levels and a marked activation of the non-canonical NF-κB pathway, with no differences in CXC-chemokines such as MIP-2 or LIX. These results show that MMP-8 can modulate the levels of S100A8 and S100A9 and its absence promotes the lung inflammatory response during endotoxemia.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
3.7
作者：
García-Prieto E;González-López A;Cabrera S;Astudillo A;Gutiérrez-Fernández A;Fanjul-Fernandez M;Batalla-Solís E;Puente XS;Fueyo A;López-Otín C;Albaiceta GM
通讯作者：
Albaiceta GM
影响因子：
4.4
作者：
Gueders, MM;Balbin, M;Cataldo, DD
通讯作者：
Cataldo, DD
影响因子：
4.8
作者：
Gutierrez-Fernandez, Ana;Inada, Masaki;Puente, Xose S.
通讯作者：
Puente, Xose S.
DOI：
10.1152/ajplung.00118.2010
发表时间：
2011-04-01
影响因子：
4.9
作者：
Yamakawa, Naoko;Uchida, Tokujiro;Makita, Koshi
通讯作者：
Makita, Koshi