The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice

Oncotarget. 2016 Sep 6;7(36):58405-58417. doi: 10.18632/oncotarget.11168.


The tripeptide-copper complex glycyl-l-histidyl-l-lysine-Cu (II) (GHK-Cu) is involved in wound healing and tissue remodeling. Although GHK-Cu exhibits anti-aging and tissue renewing properties, its roles in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are still unknown. Therefore, we examined the effects of GHK-Cu in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro and ALI in mice in vivo. GHK-Cu treatment reduced reactive oxygen species (ROS) production, increased superoxide dismutase (SOD) activity while decreased TNF-α and IL-6 production through the suppression of NF-κB p65 and p38 MAPK signaling in vitro and in vivo model of ALI. Moreover, GHK-Cu attenuated LPS-induced lung histological alterations, suppressed the infiltration of inflammatory cells into the lung parenchyma in LPS-induced ALI in mice. Taken together, these findings demonstrate that GHK-Cu possesses a protective effect in LPS-induced ALI by inhibiting excessive inflammatory responses; accordingly it may represent a novel therapeutic approach for ALI/ARDS.

Keywords: GHK-Cu; NF-κB p65; acute lung injury; inflammation; p38 MAPK.

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism
  • Animals
  • Antioxidants / metabolism
  • Cell Proliferation
  • Immune System
  • Inflammation
  • Lipopolysaccharides
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oligopeptides / chemistry*
  • Permeability
  • Peroxidase / metabolism
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • Respiratory Distress Syndrome / metabolism
  • Superoxide Dismutase / metabolism
  • Transcription Factor RelA / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Antioxidants
  • Lipopolysaccharides
  • Oligopeptides
  • Reactive Oxygen Species
  • Rela protein, mouse
  • Transcription Factor RelA
  • glycyl-histidyl-lysine
  • Peroxidase
  • Superoxide Dismutase
  • p38 Mitogen-Activated Protein Kinases