MMP-8 Deficiency Increases TLR/RAGE Ligands S100A8 and S100A9 and Exacerbates Lung Inflammation during Endotoxemia

被引：19

作者：

Gonzalez-Lopez, Adrian ^{[1
]}

Aguirre, Alina ^{[1
]}

Lopez-Alonso, Ines ^{[1
]}

Amado, Laura ^{[2
]}

Astudillo, Aurora ^{[3
]}

Soledad Fernandez-Garcia, Maria ^{[3
]}

Suarez, Maria F. ^{[4
]}

Batalla-Solis, Estefania ^{[1
,2
]}

Colado, Enrique ^{[5
]}

Albaiceta, Guillermo M. ^{[1
,2
,6
]}

机构：

[1] Univ Oviedo, Inst Univ Oncol Principado Asturias, Dept Biol Func, Oviedo, Spain

[2] Hosp Univ Cent Asturias, Serv Med Intens, Oviedo, Spain

[3] Hosp Univ Cent Asturias, Serv Anat Patol, Oviedo, Spain

[4] Univ Oviedo, Inst Univ Oncol Principado Asturias, Dept Bioquim & Biol Mol, Oviedo, Spain

[5] Hosp Univ Cent Asturias, Serv Hematol & Hemoterapia, Oviedo, Spain

[6] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain

来源：

PLOS ONE | 2012年 / 7卷 / 06期

关键词：

MATRIX METALLOPROTEINASE-8; PROTEINS; INJURY; NEUTROPHILS; INHIBITION; MICE;

D O I：

10.1371/journal.pone.0039940

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-1 alpha levels and a marked activation of the non-canonical NF-kappa B 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.

引用

页数：10

共 29 条

[1] Lack of matrix metalloproteinase-9 worsens ventilator-induced lung injury [J].