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

Abstract

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.

• Authors: Jeong-Ran Park, Hanbyeol Lee, Seok-In Kim, Se-Ran Yang
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 36 Pg. 58405-58417 (Sep 06 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27517151 (Publication Type: Journal Article)

Chemical References

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

Topics

• Acute Lung Injury (drug therapy, 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)