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

// Jeong-Ran Park 1, 2 , Hanbyeol Lee 1 , Seok-In Kim 3 , Se-Ran Yang 1 1 Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea 2 Institute of Medical Science, Kangwon National University, Chuncheon, Republic of Korea 3 Bioceltran Co., Ltd., Chuncheon, Republic of Korea Correspondence to: Se-Ran Yang, email: seran.yang@gmail.com , seran@kangwon.ac.kr Keywords: GHK-Cu, acute lung injury, inflammation, NF-κB p65, p38 MAPK Received: April 28, 2016     Accepted: July 28, 2016     Published: August 10, 2016 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.