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L-4F Inhibits Oxidized Low-density Lipoprotein-induced Inflammatory Adipokine Secretion via Cyclic AMP/Protein Kinase A-ccaat/enhancer binding Protein β Signaling Pathway in 3T3-L1 Adipocytes

引用

Chinese Medical Journal 2016年第9期129卷 1108-1112页

作者： Xiang-Zhu Xie Xin Huang Shui-Ping Zhao Bi-Lian Yu Qiao-Qing Zhong Jian Cao Department of Geriatric Cardiology Chinese PLA General Hospital Beijing 100853 China Postgraduate Department Chinese PLA Medical School Beijing 100853 China Department of Cardiology The Second XiangYa Hospital of Central South Univeisit-y Changsha Hunan 410011 China

Background： Adipocytes behave like a rich source of pro-inflammatory cytokines including monocyte chemoattractant protein- 1 （MCP- 1）. Oxidized low-density lipoprotein （oxLDL） participates in the local chronic inflammatory response, and high-density lipoprotein could counterbalance the proinftammatory function of αLDL, but the underlying mechanism is not completely understood. This study aimed to evaluate the effect of apolipoprotein A-I mimetic peptide L-4F on the secretion and expression of MCP-1 in fully differentiated 3T3-L 1 adipocytes induced by oxLDL and to elucidate the possible mechanisms. Methods： Fully differentiated 3T3-L 1 adipocytes were incubated in the medium containing various concentration of L-4F （0-50 gg/ml） with oxLDL （50 Lag/ml） stimulated, with/without protein kinase A （PKA） inhibitor H-89 （10 gmol/L） preincubated. The concentrations of MCP- 1 in the supematant, the mRNA expression of MCP- 1, the levels of ccaat/enhancer binding protein α （C/EBPα）, and ccaat/ enhancer binding protein 13 （C/EBPβ） were evaluated. The monocyte chemotaxis assay was performed by micropore filter method using a modified Boyden chamber. Results： OxLDL stimulation induced a significant increase ofMCP-1 expression and secretion in 3T3-L 1 adipocytes, which were inhibited by L-4F preincubation in a dose-dependent manner. PKA inhibitor H-89 markedly reduced the oxLDL-induced MCP-1 expression, but no further decrease was observed when H-89 was used in combination with L-4F （50 μg/ml）（P 〉 0.05）. OxLDL stimulation showed no significant effect on C/EBPa protein level but increased C/EBPβ protein level in a time-dependent manner. H-89 and L-4F both attenuated C/EBPI3 protein level in oxLDL-induced 3T3-L1 adipocytes. Conclusions： OxLDL induces C/EBPI3 protein synthesis in a time-dependent manner and enhances MCP-1 secretion and expression in 3T3-L 1 adipocytes. L-4F dose-dependently counterbalances the pro-inflammatory effect of oxLDL, and cyclic AMP/PKA-C/EBP-β signaling pat

关键词： Adipocytes ccaat/enhancer-binding proteins L-4F Monocyte Chemoattractant Protein-1 Oxidized low-densityLipoprotein Protein Kinase A

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