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4F, apolipoprotein AI mimetic peptide, attenuates acute lung injury and improves survival in endotoxemic rats

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Authors
Kwon, Woon Yong; Suh, Gil Joon; Kim, Kyung Su; Kwak, Young Ho; Kim, Kyuseok
Issue Date
2012-01
Publisher
Lippincott, Williams & Wilkins
Citation
Journal of Trauma and Acute Care Surgery, Vol.72 No.72, pp. 1576-1583
Keywords
의약학Peptide L-4Fendotoxemiaacute lung injurysurvival
Abstract
BACKGROUND: 4F, apolipoprotein AI mimetic peptide, mimics anti-inflammatory properties of high-density lipoprotein (HDL). The aim of this study was to investigate whether 4F attenuates acute lung injury and improves survival in endotoxemic rats and to determine whether the therapeutic benefits of 4F are associated with the stimulation of sphingosine-1-phosphate receptor 1 (S1P1), the activation of Akt, the down-regulation of the nuclear factor-JB (NF-JB) pathway, and the suppression of cell adhesion molecules. METHODS: To induce endotoxemia in rats, lipopolysaccharide (LPS, 10 mg/kg) was injected into a tail vein and 10 minutes later, vehicle or 4F (10 mg/kg) was administered intraperitoneally, respectively. We observed the survival of subjects for 72 hours. At 6-hour post-LPS, we killed animals and measured S1P1 expression, phosphorylated Akt/Akt ratio, cytoplasmic phosphorylated inhibitor JB->/inhibitor JB-> ratio, nuclear NF-JB p65 expression and DNA-binding activity, endothelial leukocyte adhesion molecule-1 (E-selectin) and intercellular adhesion molecule-1 expression, myeloperoxidase activity, and histologic damages in lung tissues. We also measured serum HDL cholesterol level. RESULTS: 4F improved survival in endotoxemic rats. 4F restored LPS-induced diminution of serum HDL cholesterol level and increased lung S1P1 expression and phosphorylated Akt/Akt ratio in LPS-treated rats. Furthermore, 4F suppressed inhibitor JB-> degradation, NF-JB activation, E-selectin and intercellular adhesion molecule-1 expression, and myeloperoxidase activity, and attenuated histologic damages in lung tissues. CONCLUSIONS: 4F attenuated acute lung injury and improved survival in endotoxemic rats. The therapeutic benefits of 4F were found to be associated with the stimulation of S1P1, the activation of Akt, the down-regulation of the NF-JB pathway, and the suppression of cell adhesion molecules.
ISSN
2163-0755
Language
English
URI
http://hdl.handle.net/10371/93514
DOI
https://doi.org/10.1097/TA.0b013e3182493ab4
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College of Medicine/School of Medicine (의과대학/대학원)Emergency Medicine (응급의학전공)Journal Papers (저널논문_응급의학전공)
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