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Updated: May 20, 2026
An IL-8 Transiently Transgenized Mouse Model for the In Vivo Long-term Monitoring of Inflammatory Responses
Published on: July 7, 2017
MMP-8 deficiency increases TLR/RAGE ligands S100A8 and S100A9 and exacerbates lung inflammation during endotoxemia
Adrián González-López1, Alina Aguirre, Inés López-Alonso
1Departamento de Biología Funcional, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain.
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.
Insights
Matrix metalloproteinase-8 (MMP-8) absence exacerbates lung inflammation during endotoxemia. MMP-8 deficiency increases alarmins S100A8/S100A9 and activates NF-κB, highlighting MMP-8
Area of Science:
- Immunology
- Biochemistry
- Molecular Biology
Background:
- Matrix metalloproteinase-8 (MMP-8) is a key regulator of inflammation, primarily released by neutrophils.
- Its role in modulating inflammatory mediators and its specific involvement in endotoxemia models require further elucidation.
Purpose of the Study:
- To investigate the role of MMP-8 in an experimental model of endotoxemia.
- To identify downstream inflammatory mediators affected by MMP-8 deficiency.
Main Methods:
- Endotoxemia was induced by intraperitoneal lipopolysaccharide (LPS) injection in wildtype and MMP-8 knockout mice.
- Lung inflammatory response, neutrophilic infiltration, and protein levels of alarmins (S100A8, S100A9) and chemokines (MIP-1α, MIP-2, LIX) were analyzed.
- Proteomic approaches and Western blotting were employed to assess molecular differences.
Main Results:
- Mice lacking MMP-8 exhibited a heightened lung inflammatory response and increased neutrophilic infiltration following LPS administration.
- Proteomic analysis revealed significantly elevated levels of S100A8 and S100A9 alarmins in the lungs of MMP-8 deficient mice.
- Elevated MIP-1α levels and activation of the non-canonical NF-κB pathway were observed in MMP-8 knockout mice, without changes in CXC-chemokines.
Conclusions:
- MMP-8 plays a crucial role in modulating the levels of S100A8 and S100A9.
- The absence of MMP-8 potentiates the lung inflammatory response during endotoxemia, partly through increased alarmin expression and NF-κB activation.
