Lack of matrix metalloproteinase 3 in mouse models of lung injury ameliorates the pulmonary inflammatory response in female but not in male mice.

Abstract

BACKGROUND:

The acute respiratory distress syndrome (ARDS) is a complex pulmonary disorder in which the local release of cytokines and chemokines appears central to the pathophysiology.

OBJECTIVE:

Based on the known role of matrix metalloproteinase-3 (MMP3) in inflammatory processes, the objective was to examine the role of MMP3 in the pathogenesis of ARDS through the modulation of pulmonary inflammation.

MATERIALS AND METHODS:

Female and male, wild type (MMP3+/+) and knock out (MMP3-/-) mice were exposed to two, clinically relevant models of ARDS including (i) lipopolysaccharide (LPS)-induced lung injury, and (ii) hydrochloric acid-induced lung injury. Parameters of lung injury and inflammation were assessed through measurements in lung lavage including total protein content, inflammatory cell influx, and concentrations of mediators such as TNF-α, IL-6, G-CSF, CXCL1, CXCL2, and CCL2. Lung histology and compliance were also evaluated in the LPS model of injury.

RESULTS:

Following intra-tracheal LPS instillation, all mice developed lung injury, as measured by an increase in lavage neutrophils, and decrease in lung compliance, with no overall effect of genotype observed. Increased concentrations of lavage inflammatory cytokines and chemokines were also observed following LPS injury, however, LPS-instilled female MMP3-/- mice had lower levels of inflammatory mediators compared to LPS-instilled female MMP3+/+ mice. This effect of the genotype was not observed in male mice. Similar findings, including the MMP3-related sex differences, were also observed after acid-induced lung injury.

CONCLUSION:

MMP3 contributes to the pathogenesis of ARDS, by affecting the pulmonary inflammatory response in female mice in relevant models of lung injury.

• Authors: Valeria Puntorieri, Lynda A McCaig, Christopher J Howlett, Li-Juan Yao, James F Lewis, Cory M Yamashita, Ruud A W Veldhuizen
• Journal: Experimental lung research (Exp Lung Res) Vol. 42 Issue 7 Pg. 365-379 (09 2016) ISSN: 1521-0499 [Electronic] England
• PMID: 27676418 (Publication Type: Journal Article)

Chemical References

• Lipopolysaccharides
• Matrix Metalloproteinase 3
• Mmp3 protein, mouse
• Hydrochloric Acid

Topics

• Acute Lung Injury (chemically induced)
• Animals
• Female
• Humans
• Hydrochloric Acid (pharmacology)
• Lipopolysaccharides (pharmacology)
• Male
• Matrix Metalloproteinase 3 (genetics, pharmacology)
• Mice
• Pneumonia (chemically induced)
• Respiratory Distress Syndrome (etiology)
• Sex Factors