Ac-hE-18A-NH2 inhibits the inflammatory response induced by ox-LDL via inhibiting NF-κB activation in RAW264.7 macrophages.
10.11817/j.issn.1672-7347.2014.03.002
- Author:
Qiong XIE
1
;
Feng LI
;
Shuiping ZHAO
Author Information
1. Department of Cardiology, People's Hospital of Hunan, Changsha 410005,China.
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter 1;
metabolism;
Animals;
Cell Line;
Cholesterol;
metabolism;
Gene Expression Regulation;
I-kappa B Proteins;
metabolism;
Inflammation;
metabolism;
Lipoproteins;
pharmacology;
Lipoproteins, LDL;
Macrophages;
metabolism;
Mice;
NF-kappa B;
metabolism;
Peptide Fragments;
pharmacology;
Signal Transduction;
Tumor Necrosis Factor-alpha;
metabolism
- From:
Journal of Central South University(Medical Sciences)
2014;39(3):232-238
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To evaluate the effect of Ac-hE-18A-NH2 on TNF-α secretion and mRNA expression in ox-LDL-stimulated RAW264.7 macrophages and to elucidate the possible mechanisms.
METHODS:Macrophages were incubated in the medium containing various concentrations of Ac-hE18A-NH2 (1-50 μg/mL) with ox-LDL (50 μg/mL) stimulated. The TNF-α level and intracellular cholesterol content were measured by commercially available quantitation kits following the manufacturer's instructions. TNF-α and ATP-binding cassette transporter A1 (ABCA1) mRNA expression were detected by real-time PCR. ABCA1 and IκB protein -expression in the macrophages were determined by Western blot. NF-κB activity was evaluated by electrophoretic mobility shift assay (EMSA).
RESULTS:Ox-LDL stimulation induced a significant increase in TNF-α secretion, mRNA expression, cholesterol accumulation and nuclear factor-κB (NF-κB) activity in RAW264.7 macrophages. Ac-hE-18A-NH2 reduced TNF-α secretion and mRNA expression, up-regulated the ABCA1 mRNA and protein expression, reduced the intracellular cholesterol content, and inhibited NF- κB activation in a dose-dependent manner. Under the same condition and the same concentration, Ac-hE-18A-NH2 was more efficient than D-4F (apoA-I mimetic peptide) in inhibiting the inflammatory response induced by ox-LDL in the macrophages.
CONCLUSION:Ac-hE-18A-NH2 may suppress TNF-α secretion and mRNA expression in ox-LDL stimulated RAW264.7 macrophages via IκB-NF-κB signaling pathway. The anti-inflammatory effect of Ac-hE-18A-NH2 is better than that of apoA-I mimic peptide D-4F.
