Effects of transglutaminase 2 inhibition on ventilator-induced lung injury

J Korean Med Sci. 2014 Apr;29(4):556-63. doi: 10.3346/jkms.2014.29.4.556. Epub 2014 Apr 1.

Abstract

This study was performed to examine the role of transglutaminase 2 (TG2) in ventilator-induced lung injury (VILI). C57BL/6 mice were divided into six experimental groups: 1) control group; 2) lipopolysaccharide (LPS) group; 3) lung protective ventilation (LPV) group; 4) VILI group; 5) VILI with cystamine, a TG2 inhibitor, pretreatment (Cyst+VILI) group; and 6) LPV with cystamine pretreatment (Cyst+LPV) group. Acute lung injury (ALI) score, TG2 activity and gene expression, inflammatory cytokines, and nuclear factor-κB (NF-κB) activity were measured. TG2 activity and gene expression were significantly increased in the VILI group (P < 0.05). Cystamine pretreatment significantly decreased TG2 activity and gene expression in the Cyst+VILI group (P < 0.05). Inflammatory cytokines were higher in the VILI group than in the LPS and LPV groups (P < 0.05), and significantly lower in the Cyst+VILI group than the VILI group (P < 0.05). NF-κB activity was increased in the VILI group compared with the LPS and LPV groups (P < 0.05), and significantly decreased in the Cyst+VILI group compared to the VILI group (P = 0.029). The ALI score of the Cyst+VILI group was lower than the VILI group, but the difference was not statistically significant (P = 0.105). These results suggest potential roles of TG2 in the pathogenesis of VILI.

Keywords: Acute Lung Injury; Inflammation; Respiration, Artificial; Respiratory Distress Syndrome, Adult; Transglutaminase 2; Ventilator-Induced Lung Injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / pathology
  • Animals
  • Cystamine / therapeutic use
  • Cytokines / analysis
  • Enzyme Inhibitors / therapeutic use
  • Enzyme-Linked Immunosorbent Assay
  • GTP-Binding Proteins / antagonists & inhibitors*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism
  • Gene Expression
  • Lipopolysaccharides / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Protein Glutamine gamma Glutamyltransferase 2
  • Respiration, Artificial
  • Transglutaminases / antagonists & inhibitors*
  • Transglutaminases / genetics
  • Transglutaminases / metabolism
  • Ventilator-Induced Lung Injury / enzymology*
  • Ventilator-Induced Lung Injury / pathology
  • Ventilator-Induced Lung Injury / prevention & control

Substances

  • Cytokines
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • NF-kappa B
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins
  • Cystamine