title: MMP-8 deficiency increases TLR/RAGE ligands S100A8 and S100A9 and exacerbates lung inflammation during endotoxemia.
abstract: 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.
authors: Departamento de Biología Funcional, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain.
authors: Adrián
authors: A
authors: González-López
authors: Alina
authors: A
authors: Aguirre
authors: Inés
authors: I
authors: López-Alonso
authors: Laura
authors: L
authors: Amado
authors: Aurora
authors: A
authors: Astudillo
authors: María Soledad
authors: MS
authors: Fernández-García
authors: María F
authors: MF
authors: Suárez
authors: Estefanía
authors: E
authors: Batalla-Solís
authors: Enrique
authors: E
authors: Colado
authors: Guillermo M
authors: GM
authors: Albaiceta
mesh_terms: D000818:Animals; D040501:Calgranulin A / Q000378:metabolism*; D040502:Calgranulin B / Q000378:metabolism*; D019446:Endotoxemia / Q000150:complications / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D005838:Genotype; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000172:deficiency* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011014:Pneumonia / Q000150:complications / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D040901:Proteomics; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D008024:Ligands; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C576329:S100A9 protein, mouse; C086145:S100a8 protein, mouse; D051193:Toll-Like Receptors; D020778:Matrix Metalloproteinase 2; C576328:MMP8 protein, mouse; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9