title: 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: Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.|Institute of Medical Science, Kangwon National University, Chuncheon, Republic of Korea.
authors: Jeong-Ran
authors: JR
authors: Park
authors: Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.
authors: Hanbyeol
authors: H
authors: Lee
authors: Bioceltran Co., Ltd., Chuncheon, Republic of Korea.
authors: Seok-In
authors: SI
authors: Kim
authors: Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kangwon National University, Chuncheon, Republic of Korea.
authors: Se-Ran
authors: SR
authors: Yang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D049109:Cell Proliferation; D007107:Immune System; D007249:Inflammation; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000737:chemistry*; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D009842:Oligopeptides; D017382:Reactive Oxygen Species; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; C020905:glycyl-histidyl-lysine; D009195:Peroxidase; D013482:Superoxide Dismutase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: GHK-Cu; NF-κB p65; acute lung injury; inflammation; p38 MAPK