Upregulation of matrix metalloproteinase 9 (MMP9)/tissue inhibitor of metalloproteinase 1 (TIMP1) and MMP2/TIMP2 ratios may be involved in lipopolysaccharide-induced acute lung injury

J Int Med Res. 2020 Apr;48(4):300060520919592. doi: 10.1177/0300060520919592.

Abstract

Objective: This study aimed to examine the changes and significance of matrix metalloproteinase 9 (MMP9), MMP2, tissue inhibitor of metalloproteinase 1 (TIMP1), and TIMP2 in rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI).

Methods: Wistar rats were randomly divided into a control group (injected with saline) and an ALI group (injected with LPS), then subdivided into four time points (2, 6, 12, and 24 hours). Serum tumor necrosis factor alpha and interleukin-6 levels were detected by ELISA to investigate the inflammatory reaction after LPS injection. The degree of ALI was determined by hematoxylin–eosin staining of lung tissue, the lung wet/dry weight ratio, and pulmonary permeability index. Changes in lung MMP and TIMP protein and mRNA levels were detected by western blotting and quantitative real-time polymerase chain reaction.

Results: Changes in the ratios of MMP9/TIMP1 and MMP2/TIMP2 were consistent with and strongly positively associated with the lung wet/dry weight ratio, the pulmonary permeability index, and serum tumor necrosis factor alpha and interleukin-6 levels in the ALI group.

Conclusion: ALI induced by LPS may be related to upregulation of MMP9/TIMP1 and MMP2/TIMP2 ratios.

Keywords: Matrix metalloproteinase (MMP); acute lung injury; lipopolysaccharide; lungs; rat; tissue inhibitor of metalloproteinase (TIMP).

MeSH terms

  • Acute Lung Injury / metabolism*
  • Acute Lung Injury / physiopathology
  • Animals
  • Disease Models, Animal
  • Gene Expression / genetics
  • Interleukin-6 / analysis
  • Interleukin-6 / blood
  • Lipopolysaccharides / pharmacology
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 2 / physiology
  • Matrix Metalloproteinase 9 / metabolism*
  • Matrix Metalloproteinase 9 / physiology
  • Rats
  • Rats, Wistar
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / physiology
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / physiology
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / blood
  • Up-Regulation

Substances

  • Interleukin-6
  • Lipopolysaccharides
  • Tissue Inhibitor of Metalloproteinase-1
  • Tumor Necrosis Factor-alpha
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9