Atorvastatin suppresses oxidized LDL-induced dendritic cell-like differentiation of RAW264.7 cells regulated by the p38 MAPK pathway

作者：Hu, Liu-hua; Zhang, Tuo; Shao, Qin; Li, Dan-dan; Jin, Shu-xuan; Nie, Peng; Yi, Jing; He, Ben; Shen, Ling-hong^*

来源：Molecular and Cellular Biochemistry, 2012, 371(1-2): 105-113.

DOI：10.1007/s11010-012-1427-3

• Oxidized low-density lipoprotein
• Macrophage
• Dendritic cell
• Atorvastatin
• p38 MAPK

Dendritic cells (DCs) are the most potent professional antigen-presenting cells and are involved in the initiation and progression of atherosclerosis. Recent data suggest that mature macrophages differentiate into dendritic-like cells when exposed to oxidized low-density lipoprotein (oxLDL). The purpose of the present study was to determine the effect of atorvastatin on the differentiation of macrophages to DCs and the molecular mechanisms of this transition. Mouse macrophage-like RAW264.7 cell was differentiated into a dendritic-like phenotype by incubation with oxLDL in the absence or presence of atorvastatin. The results showed that atorvastatin suppressed DC-like morphologic changes in vitro as assessed by decreased expression of DC maturation markers (CD83, CD11c, CD86, major histocompatibility complex class II, and CD1d). Atorvastatin also inhibited other oxLDL-induced functional changes including endocytic activity, ability to induce T cell proliferation, and cytokine secretion. Western blot analysis showed that oxLDL treatment of RAW264.7 cells induced phosphorylation of p38 mitogen-activated protein kinase (MAPK). However, blocking p38 MAPK with SB203580 significantly downregulated the expression of DC maturation markers, accompanied by decreased cytokine secretion. The findings of the present work demonstrate that that atorvastatin suppresses the oxLDL-induced DC-like differentiation of RAW264.7 cells by inactivating the p38 MAPK signaling pathway.

• 出版日期2012-12
• 单位河北医科大学; 上海交通大学