The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice
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Jeong-Ran Park1,2, Hanbyeol Lee1, Seok-In Kim3, Se-Ran Yang1
1Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea
2Institute of Medical Science, Kangwon National University, Chuncheon, Republic of Korea
3Bioceltran Co., Ltd., Chuncheon, Republic of Korea
Keywords: GHK-Cu, acute lung injury, inflammation, NF-κB p65, p38 MAPK
Received: April 28, 2016 Accepted: July 28, 2016 Published: August 10, 2016
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.
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