南方医科大学学报

南方医科大学学报 ›› 2017, Vol. 37 ›› Issue (12): 1563-.

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ABCA1敲低对小鼠巨噬细胞中Pam3CSK4引起的炎症反应的双向调节作用

李玥，蓝茜，武丽涛，杜小娟，Ezra Kombo Osoro，李冬民，吕社民   

  • 出版日期:2017-12-20 发布日期:2017-12-20

Bidirectional regulation of Pam3CSK4-induced inflammatory response by ATP-binding cassette transporter A1 knockdown in mouse mononuclear macrophages in vitro

  • Online:2017-12-20 Published:2017-12-20

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摘要： 目的检测ABCA1敲低对巨噬细胞中Pam3CSK4引起的炎症应答的影响。方法构建小鼠单核巨噬细胞RAW264.7的 ABCA1敲低的稳定细胞系，以TLR2配体Pam3CSK4刺激该细胞系建立炎症反应细胞模型，在该细胞模型上检测相关促炎和 抗炎细胞因子转录水平的表达变化。结果ABCA1敲低的RAW264.7稳定细胞株在Pam3CSK4刺激后，IL-1β，TNF-α和IL-6表 达发生显著上调（P<0.01），而转录抑制因子cAMP依赖性转录因子3（ATF3）也发生显著上调（P<0.01）；与此同时，ATF蛋白家族 中其它因子ATF1，ATF2，ATF4和ATF5转录水平没有发生显著变化。结论在巨噬细胞RAW264.7中，ABCA1敲低显著上调 Pam3CSK4引起的促炎因子IL-1β，TNF-α和IL-6的表达的同时，也显著上调了具有抗炎效应的ATF3的表达，其对炎症反应的 影响可能并非是单向的促炎作用，而是发生双向的调节，而ABCA1参与上调ATF3表达的机制可能也与其ATF蛋白家族其他 成员的上游调节机制不同。

Abstract: Objective To investigate the regulatory effect of ATP-binding cassette transporter A1 (ABCA1) knockdown on inflammatory response induced by Pam3CSK4 in mouse mononuclear macrophage RAW264.7 cell line. Methods A mouse mononuclear macrophage RAW264.7 cell line with stable ABCA1 knockdown was constructed and stimulated with Toll-like receptor 2 (TLR2) ligand Pam3CSK4, and the changes in the transcriptional levels of the proinflammatory and antiinflammatory cytokines were analyzed in this cell model. Results In RAW264.7 cells, ABCA1 knockdown significantly upregulated Pam3CSK4 stimulation-induced expressions of IL-1β, TNF-α and IL-6 and also enhanced the expression of transcription factor cAMP-dependent transcription factor 3 (ATF3) without obviously affecting the expressions of the transcription factors ATF1, ATF2, ATF4 or ATF5. Conclusion ABCA1 knockdown in macrophages may have both proinflammatory and anti-inflammatory effects. ABCA1 knockdown up-regulates the transcription of ATF3 possibly through a mechanism that is different from that for the other members of the ATF protein family.