Atorvastatin suppresses oxidized LDL-induced dendritic cell-like differentiation of RAW264.7 cells regulated by the p38 MAPK pathway.
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.
Department of Cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
Liu-Hua
LH
Hu
Tuo
T
Zhang
Qin
Q
Shao
Dan-Dan
DD
Li
Shu-Xuan
SX
Jin
Peng
P
Nie
Jing
J
Yi
Ben
B
He
Ling-Hong
LH
Shen
D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism; D000069059:Atorvastatin; D051940:B7-2 Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011758:Pyrroles / Q000494:pharmacology*; D015398:Signal Transduction; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D055610:Antigens, CD1d; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011758:Pyrroles; C099252:oxidized low density lipoprotein; D000069059:Atorvastatin; D048051:p38 Mitogen-Activated Protein Kinases