Regulation of macrophage differentiation and polarization by group IVC phospholipase A2
Regulation of macrophage differentiation and polarization by group IVC phospholipase A2
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DOI：
10.1016/j.bbrc.2011.11.034
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发表时间：
2011-12-16
影响因子：
3.1
通讯作者：
Akiba, Satoshi
中科院分区：
文献类型：
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作者：
Ishihara, Keiichi;Kuroda, Asuka;Akiba, Satoshi
尽管IVC型磷脂酶A（2）（IVC-PLA（2））的细胞功能仍有待了解，但在佛波酯诱导的巨噬细胞分化过程中，人单核细胞THP-1细胞中IVC-PLA（2）的表达增加。因此，我们使用THP-1细胞检测了IVC-PLA（2）在巨噬细胞分化中的作用。建立了稳定表达IVC-PLA（2）特异性shRNA的THP-1细胞株。用佛波酯处理后，IVC-PLA（2）的敲低促进了巨噬细胞的分化和成熟，而没有补偿性诱导其他IV和VI组PLA（2）的mRNA表达。此外，用溶血磷脂酰胆碱（PLA（2）介导的水解产生的磷脂代谢物）处理可消除IVC-PLA（2）敲低对巨噬细胞分化的增强作用，表明PLA（2）活性是IVC-PLA（2）抑制巨噬细胞分化所必需的。此外，我们发现，在IVC-PLA（2）敲低的细胞中，向经典活化的M1巨噬细胞的分化是上级的，而向替代活化的M2巨噬细胞的分化被IVC-PLA（2）敲低所抑制。这些发现表明IVC-PLA（2）参与巨噬细胞分化和巨噬细胞极化的调节。(C)2011 Elsevier Inc. All rights reserved.
Although the cellular function of group IVC phospholipase A(2) (IVC-PLA(2)) remains to be understood, the expression of IVC-PLA(2) in human monocytic THP-1 cells was increased during phorbol ester-induced macrophage differentiation. We therefore examined the role of IVC-PLA(2) in macrophage differentiation using THP-1 cells. Two THP-1 cell lines stably expressing IVC-PLA(2)-specific shRNA were established. Differentiation and maturation into macrophages on treatment with phorbol ester were facilitated by knockdown of IVC-PLA(2) without the compensatory induction of mRNA expression for other group IV and VI PLA(2)s. Furthermore, the enhancement of macrophage differentiation by IVC-PLA(2)-knockdown were abolished by treatment with lysophosphatidylcholine, a metabolite of phospholipids generated by PLA(2)-mediated hydrolysis, indicating that PLA(2) activity is necessary for the inhibition of macrophage differentiation by IVC-PLA(2). Additionally, we found that the differentiation into classically activated M1 macrophage was superior in IVC-PLA(2)-knockdown cells, whereas the differentiation into alternatively activated M2 macrophage was suppressed by IVC-PLA(2)-knockdown. These findings suggest that IVC-PLA(2) is involved in regulations of macrophage differentiation and macrophage polarization. (C) 2011 Elsevier Inc. All rights reserved.